Aldose reductase,NADPH and NADP+ in normal,galactose-fed and diabetic rat lens

NADPH and NADP⁺ levels were measured in rat lens from normal controls, from galactose-fed and diabetic rats during the first week of cataract formation.The level of NADPH in normal rat lens was determined to be 12.3 ± 0.4 nmol/g wet weight, and that of NADP⁺ 4.6 ± 0.2 nmol/g wet weight. In early cataract formation NADPH levels decreased rapidly during the first 2 days and then remained stable at 76% of control for galactose-fed and 84% for diabetic rats. NADP⁺ levels increased by 38% of control for galactose-fed and 54% for diabetic rats. Calculated NADPH/NADP⁺ ratios dropped from 3.36 ± 0.21 to 1.86 ± 0.16 in galactose fed rats, and from 2.81 ± 0.15 to 1.61 ± 0.16 in diabetic rats (P < 0.001 for both experimental groups). These data are consistent with rapid NADPH oxidation during onset of lens cataracts. No significant changes in aldose reductase enzymatic activity levels were observed in either the galactosemic or the diabetic rats during the times measured.     

Intermittent hypoxia maintains glycemia in streptozotocin-induced diabetic rats

Increasing studies have shown protective effects of intermittent hypoxia on brain injury and heart ischemia. However, the effect of intermittent hypoxia on blood glucose metabolism, especially in diabetic conditions, is rarely observed. The aim of this study was to investigate whether intermittent hypoxia influences blood glucose metabolism in type 1 diabetic rats. Streptozotocin-induced diabetic adult rats and age-matched control rats were treated with intermittent hypoxia (at an altitude of 3 km, 4 h per day for 3 weeks) or normoxia as control. Fasting blood glucose, body weight, plasma fructosamine, plasma insulin, homeostasis model assessment of insulin resistance (HOMA-IR), pancreas β-cell mass, and hepatic and soleus glycogen were measured. Compared with diabetic rats before treatment, the level of fasting blood glucose in diabetic rats after normoxic treatment was increased (19.88?±?5.69 mmol/L vs. 14.79?±?5.84 mmol/L, p?<?0.05), while it was not different in diabetic rats after hypoxic treatment (13.14?±?5.77 mmol/L vs. 14.79?±?5.84 mmol/L, p?>?0.05). Meanwhile, fasting blood glucose in diabetic rats after hypoxic treatment was also lower than that in diabetic rats after normoxic treatment (13.14 ± 5.77 mmol/L vs. 19.88 ± 5.69 mmol/L, p<0.05). Plasma fructosamine in diabetic rats receiving intermittent hypoxia was significantly lower than that in diabetic rats receiving normoxia (1.28?±?0.11 vs. 1.39?±?0.11, p?<?0.05), while there were no significant changes in body weight, plasma insulin and β-cell mass. HOMA-IR in diabetic rats after hypoxic treatment was also lower compared with diabetic rats after normoxic treatment (3.48?±?0.48 vs. 3.86?±?0.42, p?<?0.05). Moreover, intermittent hypoxia showed effect on the increase of soleus glycogen but not hepatic glycogen. We conclude that intermittent hypoxia maintains glycemia in streptozotocin-induced diabetic rats and its regulation on muscular glycogenesis may play a role in the underlying mechanism.     

Chronic Cobalt Treatment Decreases Hyperglycemia in Streptozotocin-Diabetic Rats

Diabetes is a metabolic disorder characterized by elevated blood glucose levels. Although conventional treatments such as insulin and other drugs reduce blood glucose, there is still a therapeutic need for effective orally administered drugs. Trace elements like vanadium and tungstate have been successfully demonstrated to reduce blood glucose in experimental diabetes with minimal chronic complications. We investigated the anti-hyperglycemic effects of cobalt in streptozotocin-diabetic rats. Normal and diabetic rats were provided with drinking water containing 3.5 mM cobalt chloride for three weeks followed by 4 mM for four weeks. Body weights and fluid consumption were monitored on a daily basis, while food intake was recorded twice every week. Prior to termination, an oral glucose tolerance test was performed on the animals. Diabetic rats lost significant body weight (357 ± 2 gm) compared to controls (482 ± 3 gm). Body weight was further reduced by cobalt treatment (290 ± 2 gm). Although it was difficult to establish a dosing regimen without weight loss, food and fluid consumption in cobalt-treated diabetic rats improved significantly compared to untreated diabetics. Plasma glucose levels were significantly reduced with reference to diabetic controls (29.3 ± 0.9 mM) by the fourth week to a lower but still hyperglycemic level (13.6 ± 3.4 mM). Cobalt-treated diabetic rats demonstrated an enhanced ability to clear a glucose load compared to untreated diabetics. Cobalt treatment neither affected the feeding and drinking patterns nor plasma glucose in normoglycemic animals although body weights decreased compared to untreated controls. We conclude that chronic cobalt treatment decreases plasma glucose levels in STZ-diabetic rats and improves tolerance to glucose.     

A role for membrane transport in modulation of intramuscular free glutamine turnover in streptozotocin diabetic rats

We wished to examine the effects of diabetes on muscle glutamine kinetics. Accordingly, female Wistar rats (200 g) were made diabetic by a single injection of streptozotocin (85 mg/kg) and studied 4 days later; control rats received saline. In diabetic rats, glutamine concentration of gastrocnemius muscle was 33% less than in control rats: 2.60 ± 0.06 μmol/g vs. 3.84 ± 0.13 μmol/g (P < 0.001). In gastrocnemius muscle, glutamine synthetase activity (V_max) was unaltered by diabetes (approx. 235 nmol/min per g) but glutaminase V_max increased from 146 ± 29 to 401 ± 94 nmol/min per g; substrate K_m values of neither enzyme were affected by diabetes. Net glutamine efflux (AZ concentration difference × blood flow) from hindlimbs of diabetic rats in vivo was greater than control values (?30.0 ± 3.2 vs. ?1.9 ± 2.6 nmol/min per g (P < 0.001) and hindlimb NH₃ uptake was concomitantly greater (about 27 nmol/min per g). The glutamine transport capacity (V_max) of the Na-dependent System N^m in perfused hindlimb muscle was 29% lower in diabetic rats than in controls (820 ± 50 vs. 1160 ± 80 nmol/min per g (P < 0.01)), but transporter K_m was the same in both groups (9.2 ± 0.5 nM). The difference between inward and net glutamine fluxes indicated that glutamine efflux in perfused hindlimbs was stimulated in diabetes at physiological perfusate glutamine (0.5 mM); ammonia (1 mM in perfusate) had little effect on net glutamine flux in control and diabetic muscles. In Intramuscular Na⁺ was 26% greater in diabetic (13.2 μmol/g) than control muscle, but muscle K⁺ (100 μmol/g) was similar. The accelerated rate of glutamine release from skeletal muscle and the lower muscle free glutamine concentration observed in diabetes may result from a combination of; (i), a diminished Na⁺ electrochemical gradient (i.e., the net driving force for glutamine accrual in muscle falls); (ii), a faster turnover of glutamine in muscle and (iii), an increased V_max/K_m for sarcolemmal glutamine efflux.     

Insulin Resistance in Nondiabetic Morbidly Obese Patients: Effect of Bariatric Surgery

Objective: To evaluate insulin action on substrate use and insulinemia in nondiabetic class III obese patients before and after weight loss induced by bariatric surgery. Research Methods and Procedures: Thirteen obese patients (four men/nine women; BMI = 56.3 ± 2.7 kg/m²) and 13 lean subjects (five men/eight women; BMI = 22.4 ± 0.5 kg/m²) underwent euglycemic clamp, oral glucose tolerance test, and indirect calorimetry. The study was carried out before (Study I) and after (～40% relative to initial body weight; Study II) weight loss induced by Roux‐en‐Y Gastric bypass with silastic ring surgery. Results: The obese patients were insulin resistant (whole‐body glucose use = 19.7 ± 1.5 vs. 51.5 ± 2.4 μmol/min per kilogram fat‐free mass, p < 0.0001) and hyperinsulinemic in the fasting state (332 ± 86 vs. 85 ± 5 pM, p < 0.0001) and during the oral glucose tolerance test compared with the lean subjects. Fasting plasma insulin normalized after weight loss, whereas whole‐body glucose use increased (35.5 ± 3.7 μmol/min per kilogram fat‐free mass, p < 0.05 vs. Study I). The higher insulin clearance of obese did not change during the follow‐up period. Insulin‐induced glucose oxidation and nonoxidative glucose disposal were lower in the obese compared with the lean group (all p < 0.05). In Study II, the former increased slightly, whereas nonoxidative glucose disposal reached values similar to those of the control group. Fasting lipid oxidation was higher in the obese than in the control group and did not change significantly in Study II. The insulin effect on lipid oxidation was slightly improved (p = 0.01 vs. Study I). Discussion: The rapid weight loss after surgery in obese class III patients normalized insulinemia and improved insulin sensitivity almost entirely due to glucose storage, whereas fasting lipid oxidation remained high.     

Increased PC-1 phosphodiesterase activity and inhibition of glucose uptake in adipocytes of type 2 diabetic rats

This study was designed to understand the cellular mechanisms responsible for defects in the insulin-stimulated signal transduction pathway in a type 2 diabetic animal model. We examined the in vitro PC-1 phosphodiesterase activity and glucose uptake in adipose tissue of streptozotocin (STZ)-induced type 2 diabetic rats. The PC-1 activity was significantly increased in adipose tissue of diabetic rats (0.54 ± 0.08 nmol PNTP hydrolyzed/mg protein/min) compared with controls (0.29 ± 0.05 nmol PNTP hydrolyzed/mg protein/min, p < 0.05). Upon insulin stimulation (100 nM), glucose uptake in the adipose tissue of the controls (4.17 ± 1.28×10⁻⁸ μmol/mg/min) was significantly higher than that in the diabetic rats (1.26 ± 0.35×10⁻⁸; p < 0.05). These results suggest that elevated PC-1 phosphodiesterase activity and decreased glucose uptake in adipose tissues may be acquired characteristics contributing to the development of type 2 diabetes mellitus.     

High fructose intake significantly reduces kidney copper concentrations in diabetic, islet transplanted rats

Trace element status is known to be altered in the diabetic state, although the factors affecting trace element homeostasis in this condition are not well understood. The authors examined the effects of a high fructose diet (40% wt:wt) vs a control diet on the copper (Cu), zinc (Zn), and iron (Fe) concentrations in the kidney, plasma, and red blood cells of islet transplanted (TX) and shamoperated (SHAM) rats. Male, Wistar Furth rats made diabetic by streptozotocin injection (55 mg/kg, iv) were given an intraportal islet transplant (1000 islets); control animals were shaminjected, shamoperated (SHAM). Rats within TX and SHAM groups were assigned to either a high fructose diet (40% fructose, 25% cornstarch, FR) or a purified control diet (33% cornstarch, 33% dextrose, CNTL) containing identical amounts of mineral mixture for a period of 6 wk. Kidney Cu concentration was significantly elevated among hyperglycemie TXCNTL rats (224 ± 25 nmol/g wet wt), but was markedly reduced in hyperglycemic TXFR rats (109 ± 14 nmol/g) relative to normoglycemic controls. This occurred in spite of similar levels of glucose, insulin (fed and fasted), insulin secretory capacity, body weight, and food intake in the TXCNTL and TXFR groups. Among the subgroup of rats with normal glucose levels post-TX, kidney Cu levels normalized and were unaffected by dietary treatment (normoglycemic TXCNTL = 60 ± 5 nmol/g; normoglycemic TXFR = 40 ± 2 nmol/g). Kidney Cu concentrations also were unaffected by fructose feeding in SHAM animals (CNTL, 60 ± 4 nmol/g and FR, 51 ± 5 nmol/g). Kidney Zn and Fe concentrations were similar among the treatment groups. Plasma and red blood cell (RBC) Cu, Zn, and Fe concentrations were also similar among the groups. Since fructose feeding led to a substantial reduction of kidney Cu concentrations in the presence of hyperglycemia, the authors suggest that this model can be useful in examining effects of altered kidney Cu accumulation in the diabetic animal.     

Maternal zinc intake of Wistar rats has a protective effect in the alloxan-induced diabetic offspring

Zinc has a role in the synthesis, storage, and secretion of insulin, and has been suggested to be beneficial when used in the diabetic state. Effect of zinc intake in pregnant rats has been studied here on diabetized offspring. Pregnant rats were divided in two groups; the control group received normal food and water, and the experimental group received zinc sulfate during pregnancy and 3 weeks after offspring birth. Male offspring from the control (C) and experimental (E) groups were divided each in three groups: C1, fed with normal food and water; C2, diabetized with alloxan; C3, received zinc sulfate; E1, fed with normal food and water; E2, diabetized with alloxan; and E3, receiving zinc sulfate. After 30 days, the histological changes of pancreatic tissues were investigated by light microscopy. Body weight, blood glucose, serum insulin levels, food intake, water intake, and urine quantity were also compared between the groups. Water intake and urine quantity were decreased significantly (p?<?0.01and p?<?0.001) in E2 (experimental diabetic group) in comparison with C2 (control diabetic group), but there was no significant difference in the body weight in C2 in comparison with E2, while blood glucose was decreased significantly (p?<?0.001) and blood insulin level was increased significantly (p?<?0.01) in E2 in comparison with C2. Microscopic evaluation of pancreas showed that E2 were protected against alloxan-induced beta-cell degeneration. In conclusion, this work showed that maternal zinc intake may influence subsequent deleterious effects of diabetes on alloxan-diabetized offspring.     

Modest Lifestyle Intervention and Glucose Tolerance in Obese African Americans

Objective: Previous studies have demonstrated the benefit of short‐term diets on glucose tolerance in obese individuals. The purpose of this study was to evaluate the effectiveness of modest lifestyle changes in maintaining improvements in glucose tolerance induced by short‐term energy restriction in obese African Americans with impaired glucose tolerance or type 2 diabetes mellitus. Research Methods and Procedures: An intervention group (n = 45; 47 ± 1 year [mean ± SE]), 105 ± 4 kg; body mass index: 39 ± 1 kg/m²) received an energy‐restricted diet (943 ± 26 kcal/d) for 1 week, followed by a lifestyle program of reduced dietary fat (?125 kcal/d) and increased physical activity (+125 kcal/d) for 1 year. Body weight and plasma concentrations of glucose, insulin, and C‐peptide during an oral glucose tolerance test were measured at baseline, 1‐week, and 4‐month intervals. A control group (n = 24; 48 ± 1 year; 110 ± 5 kg; body mass index: 41 ± 2 kg/m²) underwent these measurements at 4‐month intervals. Results: No changes in weight or glucose tolerance were observed in the control group. The intervention group had significant (p < 0.05) improvements in body weight and glucose tolerance in response to the 1‐week diet, which persisted for 4 months (p < 0.001 vs. control for change in weight). A total of 19 subjects (42%) continued the intervention program for 1 year, with sustained improvements (weight: ?4.6 ± 1.0 kg; p < 0.001 vs. control; oral glucose tolerance test glucose area: ?103 ± 44 mM · min; p < 0.05 vs. control). Discussion: A modest lifestyle program facilitates weight loss and enables improvements in glucose tolerance to be maintained in obese individuals with abnormal glucose tolerance. However, attrition was high, despite the mild nature of the program.     

The study of renin–angiotensin–aldosterone in experimental diabetes mellitus

It is generally accepted that hypertension and other vascular pathologies increase in diabetes mellitus (DM) patients as a result of the renin–angiotensin–aldosterone (RAA) system. In this study, changes in the renin‐angiotensin‐aldosterone (RAA) system level was determined in Streptozotocin (STZ)‐injected rats. A total of 46 female Wistar albino rats (180–220 g body weight) was utilized in these experiments. STZ was given intraperitoneally to induce diabetes in rats. Streptozotocin (60 mg kg⁻¹ body weight) was dissolved in 0·1 m citrate–‐phosphate buffer (pH 4–5). The non‐diabetic rats were injected with sterilized buffer alone to act as a control group. Blood glucose levels were 398±8·2 mg dl⁻¹, 488±11·75 mg dl⁻¹ and 658±29·6 mg dl⁻¹ at days 3, 12 and 30 respectively. The level of plasma renin activity (PRA) was measured as 7·69±1·07 ng ml⁻¹ h⁻¹; 1·82±0·22 ng ml⁻¹ h⁻¹ and 0·67±0·12 ng ml⁻¹ h⁻¹ at days 3, 12 and 30, respectively. These values showed that the PRA levels are decreased with increased time period. Serum angiotensin converting enzyme (ACE, E.C. 3.4.15.1) levels were increased at days 12 and 30 (p<0·05 and p<0·005), whereas serum aldosterone levels were increased at days 3 and 12 (p<0·05). The level of urea and creatinine increased at days 12 and 30 (p<0·05 and p<0·005, respectively) when compared to the control group. The data from these experiments indicate that the PRA level decreased whereas ACE activity level increased in diabetic rats compared with the control. Aldosterone levels increased at the first stage of the experiment, but then decreased by the end of the experiment as a result of changes in renin and ACE levels. Copyright © 1999 John Wiley & Sons, Ltd.     

Effect of Insulin and Energy Restriction on the Thermic Effect of Protein in Type 2 Diabetes Mellitus

Objective: The objective of this study was to test whether the thermic effect of oral protein is blunted in poorly controlled type 2 diabetes and is corrected by normalization of glycemia with insulin and 28 days of a very‐low‐energy diet. Research Methods and Procedures: Resting energy expenditure (REE) and the thermic effect of 90 g of oral protein were measured, using indirect calorimetry, in nine (five women and four men) obese diabetic people [weight, 108 ± 10 kg; waist circumference, 123 ± 8 cm; body mass index, 40 ± 3 kg/m²] who were hyperglycemic on day 8 or euglycemic with insulin on day 16 of a weight‐maintaining diet and euglycemic on day 28 of a very low energy diet (VLED). Results were compared with those of seven (six women and one man) weight‐ and body mass index‐matched obese nondiabetic subjects with a waist circumference of 111 ± 6 cm. Substrates and hormonal responses were determined concurrently. Results: Fasting glucose was normalized in the diabetic subjects with insulin from day 9 of VLED onward. Weight decreased in both groups by 9.9 ± 0.9 kg with VLED. REE was 8 ± 2% lower with insulin treatment and decreased by another 14 ± 3% with VLED in the diabetic and by 15 ± 1% in the nondiabetic subjects by week 4. After the protein meal, the thermic response was significantly (p < 0.05) less with hyperglycemia than with insulin‐induced euglycemia, as percentage above REE (15.3 ± 1.4 compared with 21.2 ± 1.5%), as percentage of the energy content of the meal (19.5 ± 1.5 compared with 25.2 ± 1.7%), as kilocalories per 405 minutes (86 ± 5 compared with 110 ± 7), and less than in nondiabetic obese controls (21.0 ± 2.2% above REE, 24.4 ± 1.7% of energy of meal). After the VLED, the thermic effect of protein was significantly higher in both groups only as percentage above REE. The initial glucagon response was greater with hyperglycemia compared with euglycemia and post‐VLED but not compared with the nondiabetic subjects. Hyperglycemia was associated with 21 ± 4% greater urinary urea nitrogen excretion and urinary glucose losses of 134 ± 50 mmol/d. Discussion: This study shows a blunted thermic effect of protein in obese hyperglycemic type 2 diabetic subjects compared with matched nondiabetic subjects that can be corrected with insulin‐ or energy restriction‐induced euglycemia.     

Effects of Nigella sativa and its Major Constituent, Thymoquinone on Sciatic Nerves in Experimental Diabetic Neuropathy

The aim of this study was designed to investigate the possible beneficial effects of Nigella sativa (NS) and thymoquinone (TQ) on histopathological changes of sciatic nerves in streptozotocin-induced diabetic rats. The rats were randomly allotted into one of four experimental groups: A (control), B (diabetic untreated), C (diabetic treated with NS) and D (diabetic treated with TQ); each group contain ten animals. B, C and D groups received streptozotocin (STZ) to induce diabetes. The rats in NS and TQ treated groups were given NS (in a dose of 400 mg/kg body weight) and TQ (50 mg/kg body weight) once a day orally by using intra-gastric intubation for 12 weeks starting 2 days after STZ injection, respectively. Blood and tissue samples were obtained for biochemical and histopathological investigation. The treatment of both NS and TQ caused a sharp decrease in the elevated serum glucose (P < 0.01, 0.05, respectively), and an increase in the lowered serum insulin concentrations (P < 0.01, 0.05, respectively), in STZ-induced diabetic rats. STZ induced a significant decrease in the area of insulin immunoreactive β-cells (P < 0.0001). NS (P < 0.001) and TQ (P < 0.01) treatment resulted in increased area of insulin immunoreactive β-cells significantly. To date, no histopathological changes of sciatic nerves in STZ induced diabetic rats by NS and TQ treatment have been reported. In this study, histologic evaluation of the tissues in diabetic animals treated with TQ and especially NS showed fewer morphologic alterations. Myelin breakdown decreased significantly after treatment with NS and TQ. The ultrastructural features of axons also showed remarkable improvement. We believe that further preclinical research into the utility of NS and TQ may indicate its usefulness as a potential treatment on peripheral neuropathy (PN) in STZ induced diabetic rats.     

Effect of vanadium on renal Na<Superscript>+</Superscript>,K<Superscript>+</Superscript>-ATPase activity in diabetic rats: a possible role of leptin

Several researches attempt to protect diabetic patients from the development of nephropathy. Involvement of leptin and renal Na⁺,K⁺-ATPase enzyme in diabetic nephropathy (DN) development is a recent field for researches. Vanadium, as a trace element with insulin mimetic effect, may act synergistically with insulin to protect against the development of DN. Sixty male Sprague Dawley rats were divided into six groups: control group (C), vanadium control group (CV), streptozotocin-induced diabetic group (D), insulin-treated diabetic group (DI), vanadium-treated diabetic group (DV), and combined insulin and vanadium-treated diabetic group. Six weeks later, systolic blood pressure (SBP) was measured and retro-orbital blood samples were collected to estimate glycosylated hemoglobin (HbA_1c), serum sodium (Na⁺) and creatinine, blood urea nitrogen (BUN) and plasma leptin levels. Preparation of microsomal fraction of renal tissue homogenate for estimation of Na⁺,K⁺-ATPase activity was done. The D group showed a significant increase in SBP, HbA_1c, serum Na⁺, creatinine, and BUN levels and Na⁺,K⁺-ATPase activity in microsomal fraction of renal tissue homogenate while plasma leptin level decreased significantly compared with C and CV groups. Both DI and DV groups showed a significant improvement in all the above measured parameters compared with D group while there were no significant changes between the DI and DV groups. Concomitant treatment with insulin and vanadium resulted in a significant improvement in all the measured parameters compared to each alone. Vanadium in combination with insulin ameliorates DN markers and reduces renal Na⁺,K⁺-ATPase overactivity in diabetic rats. An effect that may be partially mediated through correction of hypoleptinemia observed in these animals.     

A 12‐Week Aerobic Exercise Program Reduces Hepatic Fat Accumulation and Insulin Resistance in Obese,Hispanic Adolescents

The rise in obesity‐related morbidity in children and adolescents requires urgent prevention and treatment strategies. Currently, only limited data are available on the effects of exercise programs on insulin resistance, and visceral, hepatic, and intramyocellular fat accumulation. We hypothesized that a 12‐week controlled aerobic exercise program without weight loss reduces visceral, hepatic, and intramyocellular fat content and decreases insulin resistance in sedentary Hispanic adolescents. Twenty‐nine postpubertal (Tanner stage IV and V), Hispanic adolescents, 15 obese (7 boys, 8 girls; 15.6 ± 0.4 years; 33.7 ± 1.1 kg/m²; 38.3 ± 1.5% body fat) and 14 lean (10 boys, 4 girls; 15.1 ± 0.3 years; 20.6 ± 0.8 kg/m²; 18.9 ± 1.5% body fat), completed a 12‐week aerobic exercise program (4 × 30 min/week at ≥70% of peak oxygen consumption (VO₂peak)). Measurements of cardiovascular fitness, visceral, hepatic, and intramyocellular fat content (magnetic resonance imaging (MRI)/magnetic resonance spectroscopy (MRS)), and insulin resistance were obtained at baseline and postexercise. In both groups, fitness increased (obese: 13 ± 2%, lean: 16 ± 4%; both P < 0.01). In obese participants, intramyocellular fat remained unchanged, whereas hepatic fat content decreased from 8.9 ± 3.2 to 5.6 ± 1.8%; P < 0.05 and visceral fat content from 54.7 ± 6.0 to 49.6 ± 5.5 cm²; P < 0.05. Insulin resistance decreased indicated by decreased fasting insulin (21.8 ± 2.7 to 18.2 ± 2.4 µU/ml; P < 0.01) and homeostasis model assessment of insulin resistance (HOMA_IR) (4.9 ± 0.7 to 4.1 ± 0.6; P < 0.01). The decrease in visceral fat correlated with the decrease in fasting insulin (R² = 0.40; P < 0.05). No significant changes were observed in any parameter in lean participants except a small increase in lean body mass (LBM). Thus, a controlled aerobic exercise program, without weight loss, reduced hepatic and visceral fat accumulation, and decreased insulin resistance in obese adolescents.     

Weight loss therapy improves pancreatic endocrine function in obese older adults

Objective: Obesity and aging increase the risk of type 2 diabetes (T2D). We evaluated whether weight loss therapy improves pancreatic endocrine function and insulin sensitivity in obese older adults. Methods and Procedures: Twenty‐four obese (BMI: 38 ± 2 kg/m²) older (age: 70 ± 2 years) adults completed a 6‐month randomized, controlled trial. Participants were randomized to diet and exercise (treatment group) or no therapy (control group). β‐Cell function (assessed using the C‐peptide minimal model), α‐cell function (assessed by the glucagon response to an oral glucose load), insulin sensitivity (assessed using the glucose minimal model), and insulin clearance rate were evaluated using a 5‐h modified oral glucose tolerance test. Results: Body weight decreased in the treatment group, but did not change in the control group (?9 ± 1% vs. 0 ± 1%; P < 0.001). Insulin sensitivity doubled in the treatment group and did not change in the control group (116 ± 49% vs. ?11 ± 13%; P < 0.05). Even though indices of β‐cell responsivity to glucose did not change (P > 0.05), the disposition index (DI), which adjusts β‐cell insulin response to changes in insulin sensitivity, improved in the treatment group compared with the control group (100 ± 47% vs. ?22 ± 9%; P < 0.05). The glucagon response decreased in the treatment but not in the control group (?5 ± 2% vs. 4 ± 4%; P < 0.05). Insulin secretion rate did not change (P > 0.05), but insulin clearance rate increased (51 ± 25%; P < 0.05), resulting in lower plasma insulin concentrations. Discussion: Weight loss therapy concomitantly improves β‐cell function, lowers plasma glucagon concentrations, and improves insulin action in obese older adults. These metabolic effects are likely to reduce the risk of developing T2D in this population.     

Peer review: the process

Abstract

Objectives

This study was focused on the monitoring how the anti-inflammatory substance, N¹-methylnicotinamide (MNA), could influence oxidation and glycooxidation stress markers in rats under conditions of streptozotocin (STZ)-induced diabetes mellitus.

Methods

Diabetes mellitus was induced in 60 male Wistar rats by intraperitoneal injection of STZ and after 7 days diabetic animals were allocated to five groups according to the dose of MNA administered for 7 weeks. The degree of DNA damage in lymphocytes, as well as advanced glycation endproducts (AGEs), protein carbonyls, lipid peroxides, and total antioxidant capacity (TEAC) in plasma were measured.

Results

Glycation damage to proteins (represented by AGEs level) was significantly increased in all diabetic groups compared to untreated non-diabetic animals. MNA did not affect TEAC of plasma in any group of diabetic rats. Supplementation of diabetic rats with MNA at the dose of 200 mg/kg resulted in decreased protein carbonyls (from 0.0818 ± 0.0091 to 0.0558 ± 0.0044 nmol/mg proteins; P < 0.05, n = 15) and DNA oxidation, reflected by the levels of 8-oxoG (0.6302 ± 0.085 vs. 0.9213 ± 0.108 8-oxoG/10⁶ G; P < 0.05, n = 15), compared to untreated diabetic animals.

Discussion

Our results demonstrated that MNA at suitable concentrations could influence oxidative modifications of proteins and DNA.     

In situ biomechanical properties of normal and diabetic nerves: An efficient quasi-linear viscoelastic approach

Biomechanical properties of nerves were investigated using the quasi-linear viscoelastic model. An improved parameter estimation technique based on fast convolution was developed and tested in sciatic nerves of normal and diabetic rats. In situ dynamic compression response of sciatic nerves was obtained by a modified custom-designed compression system. Six normal and five diabetic neuropathic Wistar rats were used. The model derived from the high strain rate (0.1 s^?1) data could predict the responses of lower strain rates (0.05 and 0.01 s^?1) satisfactorily. The computation time was cut down 49.0% by using the newly developed technique without increasing the root-mean-square error. The percentage of stress relaxation of the diabetic and normal rats, calculated directly from the experimental data, was not significantly different (51.03±1.96% vs. 55.97±5.89%, respectively; p=0.247). After model fitting, compared with the QLV parameters of normal nerves, the smaller parameter C for diabetic nerves (0.27±0.06 vs. 0.20±0.02, p < 0.05) indicated that diabetic nerves had a smaller amplitude of viscous response (stress relaxation). The larger parameter τ₂ of diabetic nerves (199±153 s vs. 519±337 s, p<0.05) implied that diabetic nerves needed a longer relaxation period to reach equilibrium.     

Effects of insulin on renal interstitial hydrostatic pressure and natriuretic response to volume expansion in diabetic rats

Diabetes mellitus (DM) is characterized by alterations in fluid balance and blood volume homeostasis. Renal interstitial hydrostatic pressure (RIHP) has been shown to play a critical role in mediating sodium and water excretion under various conditions. The objective of this study was to determine the effects of immediate and delayed initiation of insulin treatment on the restoration of the relationship between RIHP, natriuretic, and diuretic responses to acute saline volume expansion (VE) in diabetic rats. Diabetes was induced by an intraperitoneal injection of streptozotocin (STZ; 65 mg/kg body wt). Four groups of female Sprague-Dawley rats were studied: normal control group (C), untreated diabetic group (D), immediate insulin-treated diabetic group (DI; treatment with insulin for 2 wk was initiated immediately when diabetes was confirmed, which was 2 days after STZ injection), and delayed insulin-treated diabetic group (DDI; treatment with insulin for 2 wk was initiated 2 wk after STZ injection). RIHP and sodium and water excretions were measured before and during VE (5% body wt/30 min) in the four groups of anesthetized rats. VE significantly increased RIHP, fractional excretion of sodium (FE(Na)), and urine flow rate (V) in all groups of rats. Basal RIHP, RIHP response to VE (Delta RIHP), and FE(Na) and V responses to VE (Delta FE(Na) and Delta V) were significantly lower in the D group compared with the C group of rats. Delta RIHP was significantly higher in both DI and DDI groups compared with D group but was similar to that of the C group of rats. While in the DI group the Delta FE(Na) response to VE was restored, Delta FE(Na) was significantly increased in DDI compared with D group, but it remained lower than that of the C group. In conclusion, insulin treatment initiated immediately after the onset of diabetes restores basal RIHP and RIHP, natriuretic, and diuretic responses to VE; however, delayed insulin treatment restores the basal RIHP and RIHP response to VE but does not fully restore the natriuretic response to VE.     

Long-Term,Sustained, Lifestyle-Induced Weight Loss in Severe Obesity: the Get-Real Program

Objective: To study the long-term effectiveness of a patient-centered, multidisciplinary lifestyle intervention treatment in patients medically eligible for bariatric surgery.Methods: Using a case-control study design, we compared treatment results for 98 adults (mean body mass index [BMI], 44.2 kg/m²) with the outcomes of 148 controls (mean BMI, 43.0 kg/m²) receiving standard care. The approach included a phased triage for inclusion, followed by 12 lifestyle intervention group sessions alternating with individual visits for behavior, diet, and exercise instructions.Results: At 2 years, weight loss averaged 15.3 ± 1.4 kg (P<.0010) (12 ± 1% of initial body weight [IBW], P<.001; 21 ± 2% of excess body weight [EBW], P<.001) in an intention-to-treat (ITT) analysis; in completers, weight loss was 18.8 ± 1.5 kg (P<.001) (15 ± 1% IBW, P<.001; 26 ± 3% EBW, P<.001). A total of 42 patients lost ≥10% IBW. Controls remained weight stable (P =.35); 3% lost ≥10% IBW. Patients achieving weight loss that would be considered satisfactory for bariatric surgery included 20% who achieved ≥35% EBW loss, 29% who achieved a BMI <35 kg/m² (if starting BMI <50 kg/m²) or BMI <40 kg/m² (if starting BMI ≥50 kg/m²), and 37% who achieved EBW loss ≤50%. These values for completers were 31, 39, and 48%, respectively. In the 55 patients starting the program ≥4 years ago, weight loss maintenance of 12 ± 1% IBW (ITT, 16 ± 1% in completers) was observed.Conclusion: Substantial nonsurgical weight loss, maintained at 2 to 4 years, is achievable in severely obese patients using comprehensive lifestyle approaches; the efficacy/safety trade-off in obesity treatment is an important consideration in interpreting these results.Abbreviations: BMI = body mass index EBW = excess body weight HbA_1c = glycated hemoglobin IBW = initial body weight LOCFA = last observation carried forward analysis     

Association Between the 4 bp Proinsulin Gene Insertion Polymorphism (IVS‐69) and Body Composition in Black South African Women

The objective of the study was to examine the association between a functional 4 bp proinsulin gene insertion polymorphism (IVS‐69), fasting insulin concentrations, and body composition in black South African women. Body composition, body fat distribution, fasting glucose and insulin concentrations, and IVS‐69 genotype were measured in 115 normal‐weight (BMI <25 kg/m²) and 138 obese (BMI ≥30 kg/m²) premenopausal women. The frequency of the insertion allele was significantly higher in the class 2 obese (BMI ≥35kg/m²) compared with the normal‐weight group (P = 0.029). Obese subjects with the insertion allele had greater fat mass (42.3 ± 0.9 vs. 38.9 ± 0.9 kg, P = 0.034) and fat‐free soft tissue mass (47.4 ± 0.6 vs. 45.1 ± 0.6 kg, P = 0.014), and more abdominal subcutaneous adipose tissue (SAT, 595 ± 17 vs. 531 ± 17 cm², P = 0.025) but not visceral fat (P = 0.739), than obese homozygotes for the wild‐type allele. Only SAT was greater in normal‐weight subjects with the insertion allele (P = 0.048). There were no differences in fasting insulin or glucose levels between subjects with the insertion allele or homozygotes for the wild‐type allele in the normal‐weight or obese groups. In conclusion, the 4 bp proinsulin gene insertion allele is associated with extreme obesity, reflected by greater fat‐free soft tissue mass and fat mass, particularly SAT, in obese black South African women.