Dietary carbohydrate dictates development of Type 2 diabetes in the Nile rat

Amount and type of dietary carbohydrate (CHO), as well as the CHO:fat ratio, are thought to be critical for both the rate of development and severity of Type 2 diabetes mellitus. Thus, these nutritional considerations were examined in the previously described “spontaneous” model of diabetes and metabolic syndrome, the Nile rat. Weanling male Nile rats (n=92) were fed semipurified diets, modifying glycemic index and load by changing the amount of fiber or altering the CHO:fat ratio. Random and fasting blood glucose and body weight were assessed, and diabetes was characterized in terms of blood glucose, relevant plasma and liver parameters, food and water intake and terminal organ weights. Nile rats fed with hiCHO became more hyperglycemic than rats fed with modCHO (P<.05), while loCHO and hiCHO+hiFiber rats remained essentially normoglycemic. Liver lipid and glycogen accumulation was associated with severe hyperlipemia in diabetic rats, analogous to metabolic syndrome in humans. Advanced diabetes was linked to liver and kidney damage and elevated blood urea nitrogen with weight loss. Dispersing dietary CHO by fiber or replacing it by moderate fat (reducing the glycemic index and load) delayed the onset of diabetes but did not prevent signs of insulin resistance. A very low content of dietary CHO (high fat) seemed to prevent even these early indicators of insulin resistance. Thus, the Nile rat represents a novel CHO-sensitive model for study of Type 2 diabetes that reliably follows the course of disease in humans.     

Jejunal nutrient sensing is required for duodenal-jejunal bypass surgery to rapidly lower glucose concentrations in uncontrolled diabetes

Gastrointestinal bypass surgeries restore metabolic homeostasis in patients with type 2 diabetes and obesity(1), but the underlying mechanisms remain elusive. Duodenal-jejunal bypass surgery (DJB), an experimental surgical technique that excludes the duodenum and proximal jejunum from nutrient transit(1,2), lowers glucose concentrations in nonobese type 2 diabetic rats(2–5). Given that DJB redirects and enhances nutrient flow into the jejunum and that jejunal nutrient sensing affects feeding(6,7), the repositioned jejunum after DJB represents a junction at which nutrients could regulate glucose homeostasis. Here we found that intrajejunal nutrient administration lowered endogenous glucose production in normal rats through a gut-brain-liver network in the presence of basal plasma insulin concentrations. Inhibition of jejunal glucose uptake or formation of long chain fatty acyl-coA negated the metabolic effects of glucose or lipid, respectively, in normal rats, and altered the rapid (2 d) glucose-lowering effect induced by DJB in streptozotocin (STZ)-induced uncontrolled diabetic rats during refeeding. Lastly, in insulin-deficient autoimmune type 1 diabetic rats and STZ-induced diabetic rats, DJB lowered glucose concentrations in 2 d independently of changes in plasma insulin concentrations, food intake and body weight. These data unveil a glucoregulatory role of jejunal nutrient sensing and its relevance in the early improvement of glycemic control after DJB in rat models of uncontrolled diabetes.     

Effect of exercise training on glucose homeostasis in normal and insulin-deficient diabetic rats

The effect of 8-wk of treadmill training on plasma glucose, insulin, and lipid concentrations, oral glucose tolerance, and glucose uptake in the perfused hindquarter of normal and streptozocin-treated, diabetic Sprague-Dawley rats was studied. Diabetic rats with initial plasma glucose concentrations of 200-450 mg/dl and control rats were divided into trained and sedentary subgroups. Training resulted in lower plasma free fatty acid concentrations and increased triceps muscle citrate synthase activity in both the control and diabetic rats; triglyceride concentrations were lowered by training only in the diabetic animals. Oral glucose tolerance and both basal and insulin-stimulated glucose uptake in hindquarter skeletal muscle were impaired in the diabetic rats, and plasma glucose concentrations (measured weekly) gradually increased during the experiment. Training did not improve the hyperglycemia, impaired glucose tolerance, or decreased skeletal muscle glucose uptake in the diabetic rats, nor did it alter these parameters in the normal control animals. In considering our results and those of previous studies in diabetic rats, we propose that exercise training may improve glucose homeostasis in animals with milder degrees of diabetes but fails to cause improvement in the more severely insulin-deficient, diabetic rat.     

Dietary restriction improves systemic and muscular oxidative stress in type 2 diabetic Goto–Kakizaki rats

Type 2 diabetes is a heterogeneous metabolic disease characterized by insulin resistance and β-cell dysfunction leading to hyperglycaemia and dyslipidaemia. Dietary intervention seems to improve some of these cellular complications, namely insulin resistance. Our aim was to evaluate the effects of dietary restriction on systemic and skeletal muscle oxidative stress and insulin resistance in normal Wistar rats and Goto–Kakizaki (GK) rats, a non-obese type 2 diabetic animal model. Four-month-old normal and diabetic rats were separated in four groups. One group of each strain was maintained with ad libitum standard diet, and the other group was submitted to a dietary restriction (50% of control animals daily food intake), during 2 months. Metabolic profile, insulin resistance indexes and muscle lipids were determined. Oxidative stress parameters were also measured at systemic and muscle levels: protein carbonyl, 8-hydroxy-2′-deoxyguanosine and free 8-isoprostane. Dietary restriction improved lipid profile in both strains and urinary free 8-isoprostane and plasma carbonyl compounds in diabetic rats. An improvement of muscle triglycerides accumulation and 8-isoprostane concentration and a reduction of insulin resistance were also observed in GK rats. Our data show that dietary restriction ameliorates systemic and skeletal muscle oxidative stress state in type 2 diabetes, which is associated with improved insulin resistance.     

Antihyperlipidemic and antidiabetic effects of umbelliferone in streptozotocin diabetic rats

The aim of the study was to evaluate blood glucose and lipid lowering effects of Umbelliferone (UMB) in streptozotocin (STZ) diabetic rats. Male albino Wistar rats (180 to 200 g) were induced diabetes by administration of STZ (40 mg/kg) intraperitonially. Normal and diabetic rats were treated with UMB in 10 percent dimethyl sulfoxide (DMSO) for 45 days. Diabetic rats had increased plasma glucose and decreased insulin, total proteins (TP), and albumin in addition to decreased food intake and body weight. Elevation in total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), very low density lipoprotein cholesterol (VLDL-C), triglycerides (TG), free fatty acids (FFA), and phospholipids (PL), and reduction in high density lipoprotein cholesterol (HDL-C) in the plasma were observed. Liver and kidney tissues of diabetic rats had elevation in the levels of TC, TG, FFA, and PL. Treatment with UMB decreased plasma glucose and increased insulin, TP, and albumin apart from food intake and body weight. In UMB-treated diabetic rats, plasma and tissue TC, TG, PL and FFA, and plasma LDL-C, VLDL-C, and HDL-C reversed to near normal. Thus, reduction of blood glucose and lipid profiles indicates that UMB has antidiabetic and antihyperlipidemic effects in diabetic rats.     

Appearance and metabolic development of diabetes mellitus in the sand rat, Psammomys obesus

The aim of this study was to examine the long-term effects of synthetic chow diet on the metabolic pattern of diabetic syndrome in a large group of sand rats. Few animals had a fulminating reaction with markedly decreased glucose tolerance, low plasma insulin levels and death within 3-4 weeks. But the most of sand rats developed obesity and elevated plasma insulin levels. From the third month, 40% of sand rats presented a diabetic syndrome with hyperinsulinemia, hyperglycemia, markedly decreased glucose tolerance and insulin resistance. Plasma lipids were increased; the lipid and glycogen accumulation in the liver was high. So this diabetic syndrome can be compared to maturity onset diabetes. If this synthetic chow diet lasted more than 6 months, the most of animals lost considerable weight with a strong lipid depletion of fat stores. Serum immunoreactive insulin levels fall and the blood glucose rose over 500 mg/100 ml with glycosuria and ketonuria . The elevated triglyceride content of plasma and the lipid deposits in the liver were exaggerated; glycogen had disappeared. Animals developed an overtly insulin- dependent diabetes, the latter phase of the disease. The sand rat appears to us as a potentially interesting model for investigation both maturity onset and ketotic-type diabetic syndrome.     

Effects of Dietary Glutathione on Plasma and Liver Lipid Levels in Rats Fed on a High Cholesterol Diet

The effects of dietary glutathione (GSH) on plasma and liver lipid concentrations were investigated with rats fed on a high cholesterol diet. When graded levels of GSH, 0.75 to 5.0%, were added to the 25% casein basal diet, the plasma total cholesterol level was significantly decreased and the HDL-cholesterol level was inversely increased in all addition levels without influence on the growth of animals except for the 5% addition level; the dietary addition of 5% GSH markedly depressed the growth and food consumption of rats and caused a slight diarrhea. Plasma triglyceride and phospholipid levels were decreased by the dietary addition of GSH. The contents of cholesterol and triglyceride in the liver were decreased as the dietary addition level of GSH was increased. The dietary addition of a mixture of glutamic acid, cysteine and glycine, or cysteine alone corresponding to 2.5% GSH resulted in a cholesterol-lowering effect which could not be distinguished from the effect of GSH in rats fed on the 25% casein diet. When 1.5% GSH was added to a low (10%) casein diet, the plasma cholesterol-lowering effect of GSH was also observed and the effect was comparable to that of cysteine. These results indicate that dietary-added GSH has a plasma and liver cholesterol-lowering efficacy and that this effect is largely attributable to the cysteine residue of GSH rather than to the tripeptide itself or the other amino acid residues.     

Anti-hyperglycemic activity of zinc plus cyclo (his-pro) in genetically diabetic Goto-Kakizaki and aged rats

We previously reported that treatment of streptozotocin-induced diabetic rats with zinc plus cyclo (his-pro) (CHP) decreased fed blood glucose levels and water intake. The present study was conducted to examine the dose-dependent, acute, and chronic treatment effects of CHP on oral glucose tolerance (OGT), fed blood glucose levels, water intake, and plasma insulin levels in young and aged Sprague-Dawley (S-D) rats, nondiabetic Wistar rats, and genetically diabetic Goto-Kakizaki (G-K) rats. Acute gastric gavage of 10 mg zinc plus 1.0 mg CHP/kg body weight significantly improved OGT in 4- and 13-month-old nondiabetic S-D rats and in 2-month-old diabetic G-K rats. Young S-D and G-K rats returned to pretreatment OGT values 1 week after acute gavage of zinc plus CHP (ZC), but improved OGT values persisted for at least 1 week after gavage in aged S-D rats. OGT values and fed blood glucose decreased to the greatest extent among other treatments when G-K rats were given free access to drinking water containing 1.0 to 1.5 mg CHP/L plus 10 mg zinc/L for 2 weeks. Although food and water intake showed a tendency to decrease, no statistically significant differences were observed in young G-K rats. Plasma insulin levels and blood glucose levels in both normal and diabetic G-K rats decreased with 2-week treatment with ZC. To test the direct effects of ZC on muscle tissue, we observed the effect of various doses of ZC on normal and G-K rat muscle slices. The optimal level of CHP alone for maximal muscle glucose uptake in muscle slices from normal rats was 10 microg/mL and 5.0 microg/mL in G-K rats, and ZC stimulated glucose uptake. However, no statistically significant difference was demonstrated between normal and G-K rat tissues in this study. These results indicate that oral intake of an optimal dose of ZC stimulates blood glucose metabolism, probably by stimulating muscle glucose utilization.     

Effective control of glycemic status and toxicity in Zucker diabetic fatty rats with an orally administered vanadate compound

A novel black tea decoction containing vanadate has successfully replaced insulin in a rat model of insulin-dependent diabetes but is untested in non-insulin-dependent diabetic animals. A tea-vanadate decoction (TV) containing 30 or 40 mg sodium orthovanadate was administered by oral gavage to two groups of Zucker diabetic fatty rats and a conventional water vehicle containing 30 or 40 mg of sodium orthovanadate to two others. In the latter group receiving the 30-mg dose, vanadate induced diarrhea in 50% of the rats and death in 10%. In contrast, TV-treated rats had no incidence of diarrhea and no deaths. Symptoms were more severe in both groups with higher vanadate doses, so these were discontinued. After approximately 16 weeks, the level of vanadium in plasma and tissue extracts was negligible in a further group of untreated rats but highly elevated after vanadate treatment. Vanadium levels were not significantly different between the TV-treated diabetic rats and the diabetic rats given vanadate in a water vehicle. Over the 115 days of the study, blood glucose levels increased from approximately 17 to 25 mmol/L in untreated diabetic rats. This was effectively lowered (to <10 mmol/L) by TV treatment. Fasting blood glucose levels were 5, 7, and 20 mmol/L in control (nondiabetic, untreated), TV-treated and untreated diabetic rats, respectively. Rats required treatment with TV for only approximately 50% of the days in the study. Increase in body mass during the study was significantly lower in untreated diabetic rats (despite higher food intake) than the other groups. Body mass gain and food intake were normal in TV-treated rats. Water intake was 28 mL/rat daily in control rats, 130 mL/rat daily in untreated diabetic rats, and 52 mL/rat daily in TV-treated diabetic rats. Plasma creatinine and aspartate aminotransferase levels were significantly depressed in untreated diabetic rats, and TV treatment normalized this. Our results demonstrate that a novel oral therapy containing black tea and vanadate possesses a striking capacity to regulate glucose and attenuates complications in a rat model of type II diabetes.     

Dietary whey protein decreases food intake and body fat in rats

We investigated the effects of dietary whey protein on food intake, body fat, and body weight gain in rats. Adult (11-12 week) male Sprague-Dawley rats were divided into three dietary treatment groups for a 10-week study: control. Whey protein (HP-W), or high-protein content control (HP-S). Albumin was used as the basic protein source for all three diets. HP-W and HP-S diets contained an additional 24% (wt/wt) whey or isoflavone-free soy protein, respectively. Food intake, body weight, body fat, respiratory quotient (RQ), plasma cholecystokinin (CCK), glucagon like peptide-1 (GLP-1), peptide YY (PYY), and leptin were measured during and/or at the end of the study. The results showed that body fat and body weight gain were lower (P < 0.05) at the end of study in rats fed HP-W or HP-S vs. control diet. The cumulative food intake measured over the 10-week study period was lower in the HP-W vs. control and HP-S groups (P < 0.01). Further, HP-W fed rats exhibited lower N(2) free RQ values than did control and HP-S groups (P < 0.01). Plasma concentrations of total GLP-1 were higher in HP-W and HP-S vs. control group (P < 0.05), whereas plasma CCK, PYY, and leptin did not differ among the three groups. In conclusion, although dietary HP-W and HP-S each decrease body fat accumulation and body weight gain, the mechanism(s) involved appear to be different. HP-S fed rats exhibit increased fat oxidation, whereas HP-W fed rats show decreased food intake and increased fat oxidation, which may contribute to the effects of whey protein on body fat.     

Effects of leptin on oxidative stress in healthy and Streptozotocin-induced diabetic rats

Aims/hypothesis It is generally accepted that oxidative stress is responsible for etiology and complications of diabetes. During uncontrolled Type 1 diabetes, plasma leptin levels rapidly fall. However, it is not known whether diabetes-induced hypoleptinemia has any role in oxidative stress related to uncontrolled Type I diabetes. The present study was designed to examine the effects of leptin treatment on plasma lipid peroxidation and reduced glutathion of normal and streptozotocin(STZ)-induced diabetic rats. Methods Diabetes was induced by single injection of Streptozotocin (55 mg/kg bw). One week after induction of diabetes, rats began 5-day treatment protocol of leptin injections of (0.1 mg/kg bw i.p.) or same volume vehicle. At the end of the 5th day, rats were sacrificed by cardiac puncture under anesthesia and their plasma was taken for plasma leptin, malondialdehyde, and reduced glutathione measurements. Results Plasma leptin levels decreased in STZ-induced diabetic rats while plasma glucose, TBARS, and GSH levels increased. Plasma leptin levels were not affected with leptin treatment in both diabetic and non-diabetic rats. The elevation in plasma TBARS associated with STZ diabetes decreased with leptin treatment. Leptin also increased plasma GSH levels in diabetic rats. In non-diabetic rats, treatment with leptin did not change plasma TBARS and GSH levels. Conclusions/interpretations In conclusion, leptin treatment is able to attenuate lipid peroxidation in STZ-diabetic rats, in the onset of diabetes, by increasing the GSH levels without affecting hyperglycemia and hypoleptinemia.     

The diabetic Zucker fatty rat

A noninsulin-dependent diabetes appeared in fatty rats in our Zucker rat colony. A breeding program yielded a genetic pattern of diabetes consistent with a dominant gene not closely linked to the fatty gene. Fatty males were more frequently affected than fatty females. Since no markers could be identified for heterozygous carriers and since affected fatty rats were 6 months old when diabetes appeared, the diabetic trait could not be sustained in our small colony. Glucose tolerance tests showed that the diabetic fatty rats had little increase in plasma insulin concentration after a glucose load was administered. Plasma insulin concentrations were unchanged relative to control fatty rats. Percentage body fat and plasma triglyceride values were decreased in fatty diabetic rats relative to control fatty rats, however, consistent with insulin resistance in fat and liver. The content of pancreatic insulin was markedly decreased in the diabetic fatty rat relative to either the ad libitum or diet-restricted fatty rats. The occurrence of a genetically based diabetes in a normally outbred colony underscores the importance of genetic traits that interact with obesity in determining diabetes in rodent models.     

The effect of variable magnesium intake on potential factors influencing endurance capacity

Rats fed a magnesium (MG) deficient diet have a lower endurance capacity than rats fed Mg adequate diets. The current study evaluates the effects of marginal, moderate, and severe Mg deficiencies on physiological and biochemical changes that may contribute to the reduced endurance capacity of Mg deficient rats. Variable levels of dietary Mg (400, 200, 100, 50 μg/g) were fed for 23 d to 5-wk-old male Osborne-Mendel rats. Indirect blood pressure and heart rate were measured during dietary treatment. Forty-eight hours after an endurance test, rats were killed and sampled for plasma glucose, insulin, and triglyceride levels. Organ weights, mineral and trace element concentrations, and carcass composition were determined. Blood pressure was lower in rats fed 50 and 100 ppm Mg during the first half of the study than in controls (400 ppm Mg). There were no significant differences in blood pressure among groups at the end of the study. Heart rate was not affected by dietary Mg intake. Plasma insulin was lowered by decreasing dietary Mg; however, plasma glucose and triglyceride concentrations were not affected by dietary Mg intake. Rats fed 100 and 50 ppm Mg diets had significantly higher calcium concentrations in plasma and gastrocnemius muscle than controls. Dietary Mg variably affected tissue trace element (iron, zinc, copper, and manganese) concentrations but did not affect Mg concentrations in any organ studied. Body composition was significantly altered by dietary Mg intake. In conclusion, variable Mg intake differentially affects the parameters evaluated. Thus, the decreased endurance capacity of the Mg deficient rat is apparently not the result of a single biochemical lesion but is likely to be multifactorial.     

Relationship between visceral adiposity and intramyocellular lipid content in two rat models of insulin resistance

High visceral adiposity and intramyocellular lipid levels (IMCL) are both associated with the development of type 2 diabetes. The relationship between visceral adiposity and IMCL levels was explored in diet- and glucocorticoid-induced models of insulin resistance. In the diet-induced model, lean and fa/fa Zucker rats were fed either normal or high-fat (HF) chow over 4 wk. Fat distribution, IMCL content in the tibialis anterior (TA) muscle (IMCL(TA)), and whole body insulin resistance were measured before and after the 4-wk period. The HF diet-induced increase in IMCL(TA) was strongly correlated with visceral fat accumulation and greater glucose intolerance in both groups. The increase in IMCL(TA) to visceral fat accumulation was threefold greater for fa/fa rats. In the glucocorticoid-induced model, insulin sensitivity was impaired with dexamethasone. In vivo adiposity and IMCL(TA) content measurements were combined with ex vivo analysis of plasma and muscle tissue. Dexamethasone treatment had minimal effects on visceral fat accumulation while increasing IMCL(TA) levels approximately 30% (P < 0.05) compared with controls. Dexamethasone increased plasma glucose by twofold and increased the saturated fatty acid content of plasma lipids [fatty acid (CH2)n/omegaCH3 ratio +15%, P < 0.05]. The lipid composition of the TA muscle was unchanged by dexamethasone treatment, indicating that the relative increase in IMCL(TA) observed in vivo resulted from a decrease in lipid oxidation. Visceral adiposity may influence IMCL accumulation in the context of dietary manipulations; however, a "causal" relationship still remains to be determined. Dexamethasone-induced insulin resistance likely operates under a different mechanism, i.e., independently of visceral adiposity.     

Nesfatin-1 Stimulates Fatty-Acid Oxidation by Activating AMP-Activated Protein Kinase in STZ-Induced Type 2 Diabetic Mice

Nesfatin-1 is an anorexigenic peptide involved in energy homeostasis. Recently, nesfatin-1 was reported to decrease blood glucose level and improve insulin sensitivity in high-fat diet-fed rats. However, little information is known about the influence of nesfatin-1 on lipid metabolism either in physiological or diabetic condition. This study undertook whether nesfatin-1 was involved in the pathophysiology in Streptozotocin-induced type 2 diabetic mice (T2DM), which was induced by a combination of high-calorie diet and two low-doses Streptozotocin. We observed that plasma nesfatin-1 was significantly increased while expression of nesfatin-1 neurons were decreased in hypothalamus in diabetes group compared to only high-calorie diet control group; intravenous injection of nesfatin-1 decreased 0–1h, 0–2h, 0–3h cumulative food intake in T2DM, but 0–24h total food intake had no difference between groups. Body weight and plasma FFA were normalized after nesfatin-1(10 µg/Kg) administration for 6 days. These results suggested that nesfatin-1 improved lipid disorder in T2DM. It was found that blood glucose and insulin resistance coefficient decreased with treatment of nesfatin-1 (both in 1 µg/Kg and 10 µg/Kg doses) in diabetes mice. For further understanding the role of nesfatin-1 on lipid metabolism, we detected p-AMPK and p-ACC of skeletal muscle in T2DM using western blotting. The expression of p-AMPK and p-ACC increased when nesfatin-1 was given with doses 1 µg/Kg but not in doses 10 µg/Kg. Taken together, nesfatin-1 participated in the development of T2DM and stimulated free fatty acid utilization via AMPK-ACC pathway in skeletal muscle in T2DM.     

Regulation of liver and brain hexose monophosphate dehydrogenases by insulin and dietary intake in the female rat

Summary Liver glucose 6-phosphate dehydrogenase and phosphogluconate dehydrogenase activities were significantly decreased in both diabetic and fasted rats. Treatment of diabetic rats with insulin resulted in liver glucose 6-phosphate dehydrogenase and phosphogluconate dehydrogenase activities that were significantly greater than controls. Insulin promoted an increase in food consumption that was blocked by adrenaline. Insulin, when administered together with adrenaline, restored hepatic glucose 6-phosphate dehydrogenase and phosphogluconate dehydrogenas activities of diabetic animals to control values, without altering food consumption. Brain glucose 6-phosphate dehydrogenase and phosphogluconate dehydrogenase activities were not significantly altered by either dietary restriction, diabetes or insulin treatment. These results demonstrate a dissociation between the action of insulin on hepatic glucose 6-phosphate dehydrogenase activity and its action to increase food intake.Abbreviations NADP⁺ oxidoreductase, EC 1.1.1.49 Glucose 6-P dehydrogenase, GPD, D-glucose-6-phosphate - NADP⁺ 2-oxidoreductase (decarboxylating), EC 1.1.1.44 phosphogluconate dehydrogenase, PGD, 6-phospho-D-gluconate     

High-fat hypocaloric diet modifies carbohydrate utilization of obese rats during weight loss

The effects of fat content in the hypocaloric diet on whole body glucose oxidation and adipocyte glucose transport were investigated in two animal-feeding experiments. Diet-induced obese rats were food restricted to 75% of their previous energy intakes with either a high (45% by calorie) or a low (12% by calorie) corn oil diet for 9 wk (experiment 1) or 10 days (experiment 2). The losses of body weight (P < 0.05) and adipose depot weight (P < 0.05) were less in the 45% compared with the 12% fat group. During the dynamic phase of weight loss (day 10 of food restriction), plasma glucose and insulin concentrations were higher (P < 0.05) in the 45% than those in the 12% fat group. Whole body carbohydrate oxidation rate in response to an oral load of glucose was increased (P < 0.001) by food restriction in both dietary groups; however, carbohydrate oxidation rates were lower (P < 0.01) in the 45% than in the 12% fat-fed rats during the weight loss period. Adipocyte glucose transport was greater (P < 0.02) in the 45% than in the 12% fat group in an intra-abdominal adipose depot but not in subcutaneous fat. These data suggest that dietary fat content modifies whole body glucose oxidation and intra-abdominal adipocyte glucose uptake during weight loss.     

Soy protein isolate in the presence of cornstarch reduces body fat gain in rats

The objective of the present study was to determine the combined effects of dietary protein and carbohydrate sources on total body energy and protein and fat gains as well as on plasma insulin and glucose and tissue lipoprotein lipase activity in male Sprague-Dawley rats fed semipurified diets for 28 days. The diets varied in both protein and carbohydrate sources, namely, casein-cornstarch, casein-sucrose, soy protein isolate (SPI)-cornstarch, SPI-sucrose, cod protein-cornstarch, and cod protein-sucrose. When SPI was combined with cornstarch, lower total body energy and fat gains were observed compared with the combination of either casein and sucrose, casein and cornstarch, or SPI and sucrose. Plasma glucose and insulin concentrations in addition to total and metabolizable energy intake and body weight gain were lower in rats fed the SPI-cornstarch diet than in those fed the casein-sucrose diet. Feeding the SPI-cornstarch diet compared with feeding either the casein-cornstarch or the SPI-sucrose diet also caused lower plasma glucose concentrations and a concomitant trend (p = 0.06) to reduced energy intake and body weight gain. Therefore, the reducing effects of the SPI-cornstarch diet compared with the casein-cornstarch, the casein-sucrose, and the SPI-sucrose diets on body energy and fat gains may result from reductions in energy intake and in plasma glucose concentrations.     

大脑胰岛素信号途径受损导致2型糖尿病时阿尔茨海默病发病风险增高

大脑胰岛素不仅可调节血糖,而且可改善记忆和认知,而大脑胰岛素缺乏常导致Alzheimer病（Alzheimer’s disease, AD）的发生. 本研究检测了正常及2型糖尿病（type 2 diabetes, T2D）大鼠外周及大脑胰岛素信号传导途径,以探讨T2D时由于大脑胰岛素异常导致AD发病的可能性.以同龄正常SD大鼠为对照（CTL组）,高糖、高脂、高蛋白饮食加链脲佐菌素（streptozotocin, STZ）腹腔注射建造T2D大鼠模型（T2D组）.葡萄糖氧化酶法检测血浆血糖,放免法检测脑脊液及血浆胰岛素,免疫印迹技术检测大脑海马tau蛋白上部分位点磷酸化水平,大脑及肝脏、肌肉组织胰岛素信号传导途径中磷脂酰肌醇3 激酶（phosphatidylinositol 3 kinase, PI3K）/ 蛋白激酶B（protein kinase B,Akt)、糖原合成激酶3β（glycogen synthase kinase 3β, GSK 3β）活性. 结果显示：和对照组相比,T2D大鼠血浆葡萄糖水平及胰岛素水平显著升高,脑脊液胰岛素水平显著降低,大脑海马组织tau蛋白上所检测位点均呈过度磷酸化改变,海马及外周组织（肝脏、肌肉）胰岛素信号传导途径PI3K/Akt活性均显著下降,GSK 3β活性升高. 研究结果表明：2型糖尿病大鼠大脑胰岛素缺乏及其信号传导途径下调可能是导致阿尔茨海默病发病的重要原因.     

Differential Indicators of Diabetes-Induced Oxidative Stress in New Zealand White Rabbits: Role of Dietary Vitamin E Supplementation

Determination of reliable bioindicators of diabetes-induced oxidative stress and the role of dietary vitamin E supplementation were investigated. Blood (plasma) chemistries, lipid peroxidation (LPO), and antioxidant enzyme activities were measured over 12 weeks in New Zealand White rabbits (control, diabetic, and diabetic + vitamin E). Cholesterol and triglyceride levels did not correlate with diabetic state. PlasmaLPOwas influenced by diabetes and positively correlated with glucose concentration only, not cholesterol or triglycerides. Liver glutathione peroxidase (GPX) activity negatively correlated with glucose and triglyceride levels. Plasma and erythrocyte GPX activities positively correlated with glucose, cholesterol, and triglyceride concentrations. Liver superoxide dismutase activity positively correlated with glucose and cholesterol concentration. Vitamin E reduced plasma LPO, but did not affect the diabetic state. Thus, plasmaLPOwas the most reliable indicator of diabetes-induced oxidative stress. Antioxidant enzyme activities and types of reactive oxygen species generated were tissue dependent. Diabetes-induced oxidative stress is diminished by vitamin E supplementation.