Low glycemic load diets protect against metabolic syndrome and Type 2 diabetes mellitus in the male Nile rat

BackgroundDietary modification helps prevent and manage Metabolic Syndrome (MetS) and Type 2 Diabetes Mellitus (T2DM) in humans and Nile rats. Specifically fibrous legumes, like lentils, benefit humans, but whether this reflects a specific change in the Glycemic Load (GLoad) remains controversial. Accordingly, low-GLoad foods were tested in the glucose-sensitive Nile rat.Methods131 male Nile rats aged 3 weeks to 15 months were challenged during four experiments with 15 dietary exposures that varied Glycemic Index (GI, 36–88), GLoad (102–305/2000 kcal), and cumulative GLoad (Cum GLoad=days×GLoad, 181–537g total glucose).ResultsLentil diets with low GLoads (102, 202) prevented, delayed, reduced, even reversed the progress of MetS and T2DM as measured by blood glucose (fasting, random, and oral glucose tolerance test) and plasma lipid parameters (plasma cholesterol and triglycerides) plus necropsy findings (liver and kidney pathology plus adipose reserves). The benefit from lentils exceeded dietary factors such as macronutrient composition (%Energy from carbohydrate:fat:protein, between 70:10:20 to 40:40:20), total fiber (0–24%), or dietary caloric density (2.9–4.7 kcal/g). The benefit of a low GLoad applied equally to rats inherently susceptible or resistant to T2DM, based on random glucose above or below 75 mg/dl, respectively, during interventions of 7-17 weeks.ConclusionsMeasuring total food intake and the novel concept of Cum GLoad during growth generated strong correlations (up to r=0.93) between Cum GLoad and parameters of MetS and T2DM, especially during sexual maturation. The present experiments confirm the applicability of male Nile rats to diet-induced human T2DM, and suggest dietary compositions to deter MetS and T2DM in humans.     

Very low-carbohydrate versus isocaloric high-carbohydrate diet in dietary obese rats

Objective: The effects of a very low‐carbohydrate (VLC), high‐fat (HF) dietary regimen on metabolic syndrome were compared with those of an isocaloric high‐carbohydrate (HC), low‐fat (LF) regimen in dietary obese rats. Research Methods and Procedures: Male Sprague‐Dawley rats, made obese by 8 weeks ad libitum consumption of an HF diet, developed features of the metabolic syndrome vs. lean control (C) rats, including greater visceral, subcutaneous, and hepatic fat masses, elevated plasma cholesterol levels, impaired glucose tolerance, and fasting and post‐load insulin resistance. Half of the obese rats (VLC) were then fed a popular VLC‐HF diet (Weeks 9 and 10 at 5% and Weeks 11 to 14 at 15% carbohydrate), and one‐half (HC) were pair‐fed an HC‐LF diet (Weeks 9 to 14 at 60% carbohydrate). Results: Energy intakes of pair‐fed VLC and HC rats were less than C rats throughout Weeks 9 to 14. Compared with HC rats, VLC rats exhibited impaired insulin and glycemic responses to an intraperitoneal glucose load at Week 10 and lower plasma triacylglycerol levels but retarded loss of hepatic, retroperitoneal, and total body fat at Week 14. VLC, HC, and C rats no longer differed in body weight, plasma cholesterol, glucose tolerance, or fasting insulin resistance at Week 14. Progressive decreases in fasting insulin resistance in obese groups paralleled concomitant reductions in hepatic, retroperitoneal, and total body fat. Discussion: When energy intake was matched, the VLC‐HF diet provided no advantage in weight loss or in improving those components of the metabolic syndrome induced by dietary obesity and may delay loss of hepatic and visceral fat as compared with an HC‐LF diet.     

Characterization of Obesity Phenotypes in Psammomys Obesus (Israeli Sand Rats)

Psammomys obesus (the Israeli sand rat) has been well studied as an animal model of Type 2 diabetes. However, obesity phenotypes in these animals have not been fully characterized. We analyzed phenotypic data including body weight, percentage body fat, blood glucose and plasma insulin concentration for over 600 animals from the Psammomys obesus colony at Deakin University to investigate the relationships between body fat, body weight and Type 2 diabetes using regression analysis and general linear modelling. The body weight distribution in Psammomys obesus approximates a normal distribution and closely resembles that observed in human populations. Animals above the 75th percentile for body weight had increased body fat content and a greater risk of developing diabetes. Increased visceral fat content .was also associated with elevated blood glucose and plasma insulin concentrations in these animals. A familial effect was also demonstrated in Psammomys obesus, and accounted for 51% of the variation in body weight, and 23–26% of the variation in blood glucose and plasma insulin concentrations in these animals. Psammomys obesus represents an excellent animal model of.obesity and Type 2 diabetes that exhibits a phenotypic pattern closely resembling that observed in human population studies. The obesity described in these animals was familial in nature and was significantly associated with Type 2 diabetes.     

A novel chemically modified analogue of xenin-25 exhibits improved glucose-lowering and insulin-releasing properties

Background: Xenin-25 is a K-cell derived gut peptide with insulin-releasing activity which is rapidly degraded following release into the circulation. We hypothesized that substitution of all naturally-occurring Lys and Arg residues with Gln would lead to prolonged enzyme resistance and enhanced biological efficacy.Methods: Peptide stability was assessed using murine plasma, in vitro insulin-releasing actions evaluated in BRIN-BD11 cells and acute glucose-lowering and insulin-releasing actions examined in high fat fed mice. For sub-chronic studies, a range of metabolic parameters and pancreatic histology were assessed in high fat fed mice which had received saline vehicle or xenin-25(gln) twice-daily for 21 days.Results: In contrast to native xenin-25, xenin-25(gln) was resistant to plasma-mediated degradation and significantly stimulated insulin secretion in BRIN-BD11 cells. Acute administration of xenin-25(gln) in high fat fed mice significantly reduced blood glucose and increased plasma insulin concentrations. Twice-daily administration of xenin-25(gln) in high fat fed mice did not affect food intake, body weight or circulating insulin concentrations but significantly decreased blood glucose from day 9 onwards. Furthermore, glucose tolerance, glucose-mediated insulin secretion, insulin sensitivity and GIP-stimulated insulin-release were significantly enhanced in xenin-25(gln)-treated mice. Pancreatic immunohistochemistry revealed decreased alpha cell area with increased beta cell area and beta-to-alpha cell ratio in xenin-25(gln)-treated mice. In addition, xenin-25(gln) exerted similar beneficial actions in ob/ob mice as demonstrated by reduced blood glucose, superior glycaemic response and glucose-mediated insulin release.Conclusions: Xenin-25(gln) is resistant to plasma-mediated degradation and exerts sustained and beneficial metabolic actions in high fat fed and ob/ob mice.General significance: Glutamine (gln)-modified analogues of xenin may represent an attractive therapeutic approach for type 2 diabetes.     

Paecilomyces tenuipes extracts affect lipid and glucose metabolic parameters similarly to Cordyceps militaris extracts

Ascocarps of some species of the genus Cordyceps have long been used as a traditional medicine and food source for promoting human health. The compound cordycepin, isolated from C. militaris ascocarps (CE), show similar health effects to CE. In this study, we investigated and compared the anti-obesity and antidiabetic effects of dietary CE and Paecilomyces tenuipes ascocarps (PE) in mice. In addition, we investigated their effects on the expression of genes related to the regulation of obesity and diabetes. We found that dietary CE and PE suppressed body weight gain and fat accumulation in the liver and adipocyte tissues of mice fed a high-fat diet (HFD). Enzyme and lipid profiles induced by HFD returned to normal with CE or PE treatment. Dietary CE or PE reduced fasting blood glucose and serum insulin levels in HFD-fed mice. Finally, we show that CE and PE treatment restored to normal the hyperlipidemia- and hyperglycemia-related gene expressions in HFD-fed mice. These results indicate that dietary CE or PE exert their anti-obesity and antidiabetic effects by regulating adipogenesis and insulin signaling pathways. Finally, we show that dietary CE or PE have similar anti-obesity and antidiabetic effects even when included in a normal mouse diet. Although cordycepin is not found in PE, PE treatment improves lipid and glucose metabolic parameters in a manner similar to CE. We find that PE provides alternative potential therapeutic treatments for obesity and diabetes.     

Effects of stabilized rice bran, its soluble and fiber fractions on blood glucose levels and serum lipid parameters in humans with diabetes mellitus Types I and II

Stabilized rice bran (SRB), a source of complex carbohydrates, tocols, gamma-oryzanols, and polyphenols, was treated with carbohydrases and heat to yield two fractions, rice bran water solubles (RBWS), and rice bran fiber concentrates (RBFC). Stabilized rice bran and its fractions were fed for 60 days to insulin-dependent and noninsulin-dependent diabetes mellitus (IDDM = Type I and NIDDM = Type II) subjects to determine possible effects on serum hemoglobin, carbohydrate and lipid parameters. The Type I subjects (n = 22, 26, and 20) fed Stabilized rice bran, rice bran water solubles, and rice bran fiber concentrates plus AHA Step-1 diet reduced glycosylated hemoglobin 1%, 11%, and 10%, respectively. The fasting serum glucose levels were also reduced significantly (P < 0.01) with stabilized rice bran (9%), rice bran water solubles (29%), and rice bran fiber concentrates (19%).The Type II subjects (n = 31, and 26) fed rice bran water solubles and rice bran fiber concentrates plus AHA Step-1 diet had decreased levels of glycosylated hemoglobin (15% and 11%) and fasting glucose (33% and 22%; P < 0.001), respectively. Serum insulin levels were increased (4%) with rice bran water solubles in both types of diabetes. The reduction of glycosylated hemoglobin and a slight increase in insulin levels indicate that consumption of rice bran water solubles can control blood glucose levels in human diabetes. Serum total cholesterol, LDL-cholesterol, apolipoprotein B, and triglycerides levels were reduced with rice bran fiber concentrates in the Type I (10, 16, 10, 7%) and Type II groups (12, 15, 10, 8%), respectively. These results indicate that rice bran water solubles significantly reduces hyperglycemia (P < 0.01), whereas rice bran fiber concentrates reduces hyperlipidemia (P < 0.05) in both types of diabetes. Therefore, these natural products can be used as nutritional supplements for the control of both types of diabetes mellitus in humans.     

Amelioration of hyperlipidemia by low fat diets in chronically streptozotocin-diabetic rats

The effects of reduced dietary fat intake on plasma lipid levels were examined in diabetic rats. One week after induction of diabetes (D) with streptozotocin (65 mg/kg, iv), the animals were fed food pellets consisting of 1.5% (D1.5), 2.5% (D2.5) or 5% (D5) fat for two weeks. Irrespective of the diets, both food and water consumed by untreated diabetic rats were 2- to 5-fold greater respectively compared to normal. Plasma glucose concentrations were also similarly increased. Plasma and skeletal muscle lipid levels were significantly greater than controls in D2.5 and D5, but not in the D1.5 group. Plasma and muscle lipid concentrations correlated directly with fat consumption. In D5 rats receiving insulin treatment, plasma glucose and lipid concentrations were comparable to control values. These findings indicate that the degree of hyperlipidemia in chronically diabetic rats is directly related to dietary fat intake. They also demonstrate that dietary interventions can modulate some of the metabolic abnormalities in diabetes.     

Improved insulin sensitivity and metabolic flexibility in ghrelin receptor knockout mice

Stimulation of the ghrelin receptor (GhrR) by ghrelin results in a variety of metabolic changes including increased food intake, fat storage and insulin resistance. Loss of ghrelin signaling is protective against diet-induced obesity, suggesting that ghrelin plays a significant homeostatic role in conditions of metabolic stress. We examined glycemic control in GhrR −/− mice fed a high-fat diet, and used indirect calorimetry to assess fuel substrate usage and energy expenditure. GhrR −/− mice fed a high-fat diet had several measures of greater insulin sensitivity, including: lower fasted blood glucose and plasma insulin, lower %Hb_A1c, lower insulin levels during glucose tolerance tests, and improved performance in hyperinsulinemic-euglycemic and hyperglycemic clamp studies. GhrR −/− mice fed a high-fat diet did not develop hepatic steatosis and had lower total cholesterol, relative to controls. Furthermore, GhrR −/− mice demonstrated a lower intestinal triglyceride secretion rate of dietary lipid. GhrR −/− mice have higher respiratory quotients (RQ), indicating a preference for carbohydrate as fuel. The range of RQ values was wider in GhrR −/− mice, indicating greater metabolic flexibility and insulin sensitivity in these animals. We therefore propose that loss of ghrelin signaling promotes insulin sensitivity and metabolic flexibility, and protects against several fatty diet-induced features of metabolic syndrome due to convergent changes in the intake, absorption and utilization of energy.     

KDT501, a Derivative from Hops,Normalizes Glucose Metabolism and Body Weight in Rodent Models of Diabetes

Aims/Hypothesis

We developed KDT501, a novel substituted 1,3-cyclopentadione chemically derived from hop extracts, and evaluated it in various in vitro and in vivo models of diabetes and insulin sensitivity.

Methods

KDT501 was evaluated for anti-inflammatory effects in monocyte/macrophage cells; agonistic activity for peroxisome proliferator-activated receptors (PPAR); lipogenesis and gene expression profile in human subcutaneous adipocytes. Body composition, glucose, insulin sensitivity, and lipids were assessed in diet-induced obesity (DIO) mice and Zucker Diabetic Fatty (ZDF) rats after oral administration.

Results

KDT501 mediated lipogenesis in 3T3L1 and human subcutaneous adipocytes; however, the gene expression profile of KDT501 differed from that of the full PPARγ agonist rosiglitazone, suggesting that KDT501 has pleiotropic biological activities. In addition, KDT501 showed only modest, partial PPARγ agonist activity and exhibited anti-inflammatory effects in monocytes/macrophages that were not observed with rosiglitazone. In a DIO mouse model, oral administration of KDT501 significantly reduced fed blood glucose, glucose/insulin AUC following an oral glucose bolus, and body fat. In ZDF rats, oral administration of KDT501 significantly reduced fed glucose, fasting plasma glucose, and glucose AUC after an oral glucose bolus. Significant, dose-dependent reductions of plasma hemoglobin A1c, weight gain, total cholesterol, and triglycerides were also observed in animals receiving KDT501.

Conclusion

These results indicate that KDT501 produces a unique anti-diabetic profile that is distinct in its spectrum of pharmacological effects and biological mechanism from both metformin and pioglitazone. KDT501 may thus constitute a novel therapeutic agent for the treatment of Type 2 diabetes and associated conditions.     

The Effects of Dietary Iron and Capsaicin on Hemoglobin,Blood Glucose,Insulin Tolerance,Cholesterol, and Triglycerides,in Healthy and Diabetic Wistar Rats

ObjectiveOur aim was to assess the effects of dietary iron, and the compound capsaicin, on hemoglobin as well as metabolic indicators including blood glucose, cholesterol, triglycerides, insulin, and glucose tolerance.ResultsHealthy rats fed a low-iron diet exhibited significantly reduced total cholesterol and triglyceride levels, compared with rats fed a control diet. Significantly reduced blood lipid was also provoked by low dietary iron in diabetic rats, compared with those fed a control diet. Insulin, and glucose tolerance was only improved in healthy rats fed the low-iron diet. Significant increases in total cholesterol were found in diabetic rats fed a high-iron diet, compared with healthy rats fed the same diet, although no statistical differences were found for triglycerides. Hemoglobin levels, which were not statistically different in diabetic versus healthy rats fed the high-iron diet, fell when capsaicin was added. Capsaicin also provoked a fall in the level of cholesterol and triglycerides in diabetic animals, versus diabetics fed with the high iron diet alone. In conclusion, low levels of dietary iron reduced levels of serum triglycerides, hemoglobin, and cholesterol, and significantly improved insulin, and glucose tolerance in healthy rats. In contrast, a high-iron diet increased cholesterol significantly, with no significant changes to triglyceride concentrations. The addition of capsaicin to the high-iron diet (for diabetic rats) further reduced levels of hemoglobin, cholesterol, and triglycerides. These results suggest that capsaicin, may be suitable for the treatment of elevated hemoglobin, in patients.     

Improved n-3 fatty acid status does not modulate insulin resistance in fa/fa Zucker rats

The objective was to examine the effect of polyunsaturated fatty acid type (plant vs fish oil-derived n-3, compared to n-6 fatty acids in the presence of constant proportions of saturated, monounsaturated and polyunsaturated fatty acids) on obesity, insulin resistance and tissue fatty acid composition in genetically obese rats. Six-week-old fa/fa and lean Zucker rats were fed with a 10% (w/w) mixed fat diet containing predominantly flax-seed, menhaden or safflower oils for 9 weeks. There was no effect of dietary lipid on obesity, oral glucose tolerance (except t=60 min insulin), pancreatic function or molecular markers related to insulin, glucose and lipid metabolism, despite increased n-3 fatty acids in muscle and adipose tissue. The menhaden oil diet reduced fasting serum free fatty acids in both fa/fa and lean rats. These data suggest that n-3 composition does not alter obesity and insulin resistance in the fa/fa Zucker rat model when dietary lipid classes are balanced.     

Chronic consumption of farmed salmon containing persistent organic pollutants causes insulin resistance and obesity in mice

Background

Dietary interventions are critical in the prevention of metabolic diseases. Yet, the effects of fatty fish consumption on type 2 diabetes remain unclear. The aim of this study was to investigate whether a diet containing farmed salmon prevents or contributes to insulin resistance in mice.

Methodology/Principal Findings

Adult male C57BL/6J mice were fed control diet (C), a very high-fat diet without or with farmed Atlantic salmon fillet (VHF and VHF/S, respectively), and Western diet without or with farmed Atlantic salmon fillet (WD and WD/S, respectively). Other mice were fed VHF containing farmed salmon fillet with reduced concentrations of persistent organic pollutants (VHF/S_-POPs). We assessed body weight gain, fat mass, insulin sensitivity, glucose tolerance, ex vivo muscle glucose uptake, performed histology and immunohistochemistry analysis, and investigated gene and protein expression. In comparison with animals fed VHF and WD, consumption of both VHF/S and WD/S exaggerated insulin resistance, visceral obesity, and glucose intolerance. In addition, the ability of insulin to stimulate Akt phosphorylation and muscle glucose uptake was impaired in mice fed farmed salmon. Relative to VHF/S-fed mice, animals fed VHF/S_-POPs had less body burdens of POPs, accumulated less visceral fat, and had reduced mRNA levels of TNFα as well as macrophage infiltration in adipose tissue. VHF/S_-POPs-fed mice further exhibited better insulin sensitivity and glucose tolerance than mice fed VHF/S.

Conclusions/Significance

Our data indicate that intake of farmed salmon fillet contributes to several metabolic disorders linked to type 2 diabetes and obesity, and suggest a role of POPs in these deleterious effects. Overall, these findings may participate to improve nutritional strategies for the prevention and therapy of insulin resistance.     

Doxycycline-Regulated 3T3-L1 Preadipocyte Cell Line with Inducible,Stable Expression of Adenoviral E4orf1 Gene: A Cell Model to Study Insulin-Independent Glucose Disposal

Impaired glycemic control and excessive adiposity are major risk factors for Type 2 Diabetes mellitus. In rodent models, Ad36, a human adenovirus, improves glycemic control, independent of dietary fat intake or adiposity. It is impractical to use Ad36 for therapeutic action. Instead, we identified that E4orf1 protein of Ad36, mediates its anti-hyperglycemic action independent of insulin signaling. To further evaluate the therapeutic potential of E4orf1 to improve glycemic control, we established a stable 3T3-L1 cell system in which E4orf1 expression can be regulated. The development and characterization of this cell line is described here. Full-length adenoviral-36 E4orf1 cDNA obtained by PCR was cloned into a tetracycline responsive element containing vector (pTRE-Tight-E4orf1). Upon screening dozens of pTRE-Tight-E4orf1 clones, we identified the one with the highest expression of E4orf1 in response to doxycycline treatment. Furthermore, using this inducible system we characterized the ability of E4orf1 to improve glucose disposal in a time dependent manner. This stable cell line offers a valuable resource to carefully study the novel signaling pathways E4orf1 uses to enhance cellular glucose disposal independent of insulin.     

In-vivo hyperglycemic,antioxidant, histopathological changes,and simultaneous measurement of kaempferol verified by high-performance thin layer chromatography of Setaria italica in streptozotocin -induced diabetic rats

BackgroundSetaria italica (common name- foxtail, kangni) is one of the major food crops which is prominently cultivated in southern regions of India and in certain regions of Uttar Pradesh. Besides the crop’s consumption as a general source of carbohydrate rich cereal, the seeds of the crop are comprised of more fiber. So, it is recommended to add in the dietary supplementation of the diabetic people across the country.ObjectiveIn this paper, it intends to investigate the antidiabetic activity and antioxidant activity of S. italica (foxtail millet) seeds in diabetic rats.MethodsThe six genotypes of foxtail millets (S. italica) namely Kangni-1, Kangni-4, Kangni-5, Kangni-6, Kangni-7 & Kangni-10 respectively were subjected to in vitro investigations via. comprehensive metabolic panel (CMP) involving blood glucose study, Kidney & Liver function test, and antioxidant study (Catalase test; Glutathione S-transferase (GST); Superoxide Dismutase (SOD); glutathione (GSH); hiobarbituric acid reactive substances (TBARS) & Glutathione peroxidase (GPx) and were performed in vivo animal investigations in Wistar rats. The STZ induced diabetic rats were fed with doses of different S. italica seed aqueous extract to evaluate its anti-hyperglycemic activity by oral administration of SISAE. Further, it was compared with Glibenclamide which acts as one of the standard oral hypoglycemic agents.ResultsFrom achieved outcomes, a significant fall of blood glucose level (70%) produced 300 mg SISAE/kg b.w. after 6 h of extract administration. However, no change could be produced by these doses of the SISAE in normal rats’ blood glucose levels. A significant fall in glucose level along with significant glycemic control by lower HbA1c levels was observed in diabetic treated rats after 3 weeks of treatment with 300 mg of SISAE/kg b.w./day when comparing to untreated diabetic rats. Among these five genotypes of S. italica, the differences in the glycemic index were found. a significant fall could be found in blood glucose levels of Wistar rats, when every experimental rat was incorporating with the extract of different genotypes of Setaria italica L. Beauv than the rats treated with Glibenclamide in every 7 days of interval. The level of catalase, SOD, GST, GPx, GSH and TBARS showed variation while the rats were fed with the extract of S. italica in the liver test of rats. In kidney function test, the result shows that there is significant relationship between foxtail extract and kidney function of STZ induced diabetes rats. They show the change in their serum creatinine level, serum urea and serum uric acid.ConclusionThe result obtained from the study shows that the extract of S. italica seeds is capable for the hypolipidemic and antihyperglycemic activities, thereby, they serve as one of the good sources for herbal medicinal items.     

Increase in DPP-IV in the intestine, liver and kidney of the rat treated with high fat diet and streptozotocin

High fat diet or insulin deficiency is commonly seen in Type II diabetes, while the mechanism remains unclear. To test our hypothesis that DPP-IV contributes to Type II diabetes, we examined the expression and activity of DPP-IV in rats (n=8 to each group) treated for 12 weeks with 3 separate diets: a) normal control; b) a high fat diet; and c) a high fat diet plus streptozotocin, a chemical for induction of insulin-deficient diabetes. Compared to rats on the normal diet, the rats with a high fat diet significantly increased DPP-IV's expression and activity about 142-152% in the intestine (P<0.05) and 153-240% in kidneys (P<0.05), but there was no change in the liver. Administration of streptozotocin to the rats treated with the high fat diet showed an insufficient insulin secretion and higher blood glucose in response to glucose/insulin tolerance test, and an increase in expression of DPP-IV and activity by 188-242% in the intestine (P<0.01); 191-225% in liver (P<0.01); and 211-321% in the kidneys (P<0.01). Immunohistochemistry studies confirmed the above results, showing increased DPP-IV immunostaining localized primarily in intestinal epithelium, hepatocytes and renal tubular cells. This study, for the first time reports an increase in DPP-IV associated with a high fat diet, as well as in the combination of a high fat diet with an insulin deficiency. Since both high fat diet and insulin deficiency are closely linked with etiology of Type II diabetes, the evidence in this study suggests a role of DPP-IV in development of Type II diabetes.     

An energetic and conceptual model of the physiological role of dietary carbohydrates and salinity on Litopenaeus vannamei juveniles

We are reporting results directed to explain the relation between carbohydrates (CHO), protein metabolism, and the energetic balance of Litopenaeus vannamei juveniles. The interaction of dietary CHO and salinity was measured to try to understand the relation between osmotic control and metabolism, both from a biochemical and energetic point of view. Two experiments were done. In the first experiment, shrimp were fed with 0%, 5%, 33%, and 61% CHO and maintained at 15‰ and 40‰ salinity. Glucose, lactate protein, hemocyanin, ammonia concentration, and osmotic pressure were measured in blood. Digestive gland glycogen (DGG) was measured also. In the second experiment, shrimp were fed with 0% and 38% dietary CHO and maintained at 15‰ and 40‰ salinity. From that shrimp, absorbed energy (Abs) was calculated as: Abs=respiration (R)+ammonia excretion (U) and production (P); assimilated energy (As) was calculated as the product of R×P. Osmotic pressure, hemocyanin, protein, lactate, and blood ammonia increased with the reduction in dietary CHO. In contrast, an increase in blood glucose was observed with an increase in dietary CHO. Digestive gland glycogen (DGG) increased following a saturation curve with a DGG maximum at 33% dietary CHO. Blood metabolites of fasting and feeding shrimp showed the same behavior. Energy balance results showed that shrimp maintained in low salinity and fed without CHO waste more energy in U production than for shrimp maintained in high salinity and fed with high CHO levels. Notwithstanding, the production efficiency was higher in shrimp fed without CHO than that observed in shrimp fed with high CHO independent of salinity. A scheme trying to integrate the relation between CHO and protein metabolism and the way in which both are modulated by salinity is presented. From published and present results, there are two factors that apparently control the use of high dietary CHO levels; α-amylase enzyme-dietary CHO level capacity and glycogen saturation in DG. Production of glucose is limited in shrimp because of saturation of α-amylase when shrimp are fed with diets above 33% CHO. This is the first control point of starch metabolism. The digestive gland is saturated with glycogen in shrimp fed with dietary CHO levels >33%. This is apparently the second control point of CHO metabolism that limits growth rate in such conditions. The high metabolic cost related to high CHO diets could explain why shrimp are well adapted to use protein as a source of energy.     

Grape skin extract protects against programmed changes in the adult rat offspring caused by maternal high-fat diet during lactation

Maternal overnutrition during suckling period is associated with increased risk of metabolic disorders in the offspring. We aimed to assess the effect of Vitis vinifera L. grape skin extract (ACH09) on cardiovascular and metabolic disorders in adult male offspring of rats fed a high-fat (HF) diet during lactation. Four groups of female rats were fed: control diet (7% fat), ACH09 (7% fat plus 200 mg kg^?1 d^?1 ACH09 orally), HF (24% fat), and HF+ACH09 (24% fat plus 200 mg kg^?1 d^?1 ACH09 orally) during lactation. After weaning, all male offspring were fed a control diet and sacrificed at 90 or 180 days old. Systolic blood pressure was increased in adult offspring of HF-fed dams and ACH09 prevented the hypertension. Increased adiposity, plasma triglyceride, glucose levels and insulin resistance were observed in offspring from both ages, and those changes were reversed by ACH09. Expression of insulin cascade proteins IRS-1, AKT and GLUT4 in the soleus muscle was reduced in the HF group of both ages and increased by ACH09. The plasma oxidative damage assessed by malondialdehyde levels was increased, and nitrite levels decreased in the HF group of both ages, which were reversed by ACH09. In addition, ACH09 restored the decreased plasma and mesenteric arteries antioxidant activities of superoxide dismutase, catalase and glutathione peroxidase in the HF group. In conclusion, the treatment of HF-fed dams during lactation with ACH09 provides protection from later-life hypertension, body weight gain, insulin resistance and oxidative stress. The protective effect ACH09 may involve NO synthesis, antioxidant action and activation of insulin-signaling pathways.     

Ideglira is Associated With Improved Short-Term Clinical Outcomes and Cost Savings Compared With Insulin Glargine U100 Plus Insulin Aspart in the U.S.

Objective: In the DUAL (Dual Action of Liraglutide and Insulin Degludec in Type 2 Diabetes) VII trial, IDegLira (a combination of insulin degludec and liraglutide) was compared with insulin glargine U100 plus insulin aspart. Both treatment approaches achieved similar glycemic control, but there were differences in hypoglycemia, changes in body weight, and injection frequency. The aim of the present analysis was to assess the short-term cost effectiveness of IDegLira versus insulin glargine U100 plus insulin aspart for treatment of patients with type 2 diabetes mellitus not meeting glycemic targets on basal insulin in the U.S. setting.Methods: A cost-utility model was developed to evaluate the clinical and economic outcomes associated with the 2 treatments over a 1-year time horizon, capturing the impact on quality of life of hypoglycemic events, body mass index, and injection frequency. Costs were captured from a healthcare payer perspective in 2017 U.S. dollars ($).Results: IDegLira was associated with improved quality of life by 0.12 quality-adjusted life years compared with insulin glargine U100 plus insulin aspart. The key drivers of this difference were reduced injection frequency and hypoglycemic events avoided. IDegLira was associated with increased annual drug costs, but this was entirely offset by reduced needle costs and reduced costs of self-monitoring of blood glucose testing. IDegLira was associated with total annual cost savings of $743 per patient.Conclusion: IDegLira was found to improve quality-adjusted life expectancy and reduce costs when compared with insulin glargine U100 plus insulin aspart for treatment of patients with type 2 diabetes not achieving glycemic control on basal insulin in the U.S. setting.Abbreviations: ADA = American Diabetes Association; BMI = body mass index; CI = confidence interval; DUAL = Dual Action of Liraglutide and Insulin Degludec in Type 2 Diabetes; GLP-1 = glucagon-like peptide-1; HbA1c = glycated hemoglobin; ICER = incremental cost-effectiveness ratio; IU = international units; QALY = quality-adjusted life year; SMBG = self-monitoring of blood glucose     

阿司匹林增加胰岛素抵抗大鼠胰岛素敏感性的实验研究

目的　观察阿司匹林对高脂饮食大鼠胰岛素敏感性的影响。方法　灌服阿司匹林前后采用腹腔注射胰岛素耐量试验 (IITT)观察大鼠胰岛素的敏感性 ,并测定空服胰岛素、血糖和血脂等。结果　高脂饮食 4月、阿司匹林治疗 4周后 ,IITT发现高脂组腹腔注射胰岛素后 1h、1 5h和 2h的血糖及空腹胰岛素和甘油三酯水平显著高于正常对照组 (P <0 0 5或P <0 0 1 ) ;而阿司匹林治疗组腹腔注射胰岛素后 1h、1 5h和 2h的血糖及空腹胰岛素和甘油三酯水平显著低于高脂组 (P <0 0 5或P <0 0 1 ) ,与正常对照组差异无显著性。结论　大剂量阿司匹林有增加胰岛素敏感性和改善脂代谢紊乱的作用     

Pathway-selective Insulin Resistance and Metabolic Disease: The Importance of Nutrient Flux

Hepatic glucose and lipid metabolism are altered in metabolic disease (e.g. obesity, metabolic syndrome, and Type 2 diabetes). Insulin-dependent regulation of glucose metabolism is impaired. In contrast, lipogenesis, hypertriglyceridemia, and hepatic steatosis are increased. Because insulin promotes lipogenesis and liver fat accumulation, to explain the elevation in plasma and tissue lipids, investigators have suggested the presence of pathway-selective insulin resistance. In this model, insulin signaling to glucose metabolism is impaired, but insulin signaling to lipid metabolism is intact. We discuss the evidence for the differential regulation of hepatic lipid and glucose metabolism. We suggest that the primary phenotypic driver is altered substrate delivery to the liver, as well as the repartitioning of hepatic nutrient handling. Specific alterations in insulin signaling serve to amplify the alterations in hepatic substrate metabolism. Thus, hyperinsulinemia and its resultant increased signaling may facilitate lipogenesis, but are not the major drivers of the phenotype of pathway-selective insulin resistance.