Reduced Fasting Blood Glucose Levels Research Articles

Zengye Decoction Ameliorates Insulin Resistance by Promoting Glucose Uptake.

The incidence of type 2 diabetes mellitus (T2DM) has been increasing in recent years and has become a serious threat to human health. Zengye Decoction (ZYD), a well-known traditional Chinese medicinal formula, has been used in the treatment of T2DM with yin asthenia and extreme heat since Qing Dynasty. However, the characteristics of antidiabetic activities of ZYD have not been fully elucidated. In our study, high-fat diet and streptozotocin were used to establish the T2DM rat model. After 3 weeks of treatment with ZYD, the fasting blood glucose (FBG), oral glucose tolerance, the fasting serum insulin concentration, insulin sensitivity index (ISI), serum lipid profiles, and pancreas histopathology were measured. Then, under circumstance of insulin-resistant glucose consumption, 2-(N-(7-nitrobenz-2-oxa-l,3-diazol-4-yl) amino)-2-deoxyglucose (2-NBDG) uptake and glycogen content in C2C12 myotubes, 3T3-L1 adipocytes, and HepG2 cells were determined, respectively. Finally, the expressions of key targets in the insulin signaling pathway were measured to explain the potential mechanism underlying these activities. After administration with ZYD, a notable reduction in FBG levels, oral glucose tolerance test-area under the curve, blood lipid metabolism, and ISI values were observed compared with the diabetic control group. Moreover, ZYD restored the damaged islet cells in T2DM rats. Significant increases in glucose consumption, glucose uptake, glycogen content, expression of glucose transporter type 4, and the ratio of p-Akt/Akt were observed in the ZYD groups. According to the above results, ZYD exhibited glucose disposal, including glucose consumption, glucose uptake, and glycogen content and promoted the Akt signal pathway, which indicates that ZYD exerts significant hypoglycemic effect in T2DM.

Possible therapeutic effects of vindoline on testicular and epididymal function in diabetes-induced oxidative stress male Wistar rats

ObjectiveThe study evaluated the effects of vindoline on testicular and epididymal oxidative stress in diabetes-induced male Wistar rats. MethodsForty-eight (48), 6-week old male Wistar rats weighing between 190-230g were divided into 6 groups (n = 8) and used for this study. Group 1 was the normal control, group 2 comprised non-diabetic rats treated with vindoline, and group 3 was the non-diabetic group of rats treated with glibenclamide-the standard drug for the treatment of diabetes. Group 4 was the diabetic control, group 5 comprised diabetic rats treated with vindoline and group 6 was the diabetic rats treated with glibenclamide. Diabetes was induced in group 4, group 5 and group 6 rats by subjecting them to 10% fructose water over a period of 2 weeks, followed by administration of a single intraperitoneal injection of 40 mg/kg b.w streptozotocin (STZ). Testicular and epididymal lipid peroxidation levels, antioxidant enzymes, scavenging activity and total antioxidant capacity were measured. ResultsDiabetes-induced male Wistar rats demonstrated chronic hyperglycaemia, oxidative stress and reduced oxygen radical absorption capacity in both testicular and epididymal tissues. Short-term treatment of diabetic rats with vindoline for 5 weeks significantly reduced fasting blood glucose levels, minimise testicular oxidative stress, increased testicular and epididymal catalase and epididymal SOD and increase total antioxidant activity capacity. ConclusionTreatment with vindoline showed protective effects against diabetes-induced oxidative stress in both testicular and epididymal tissues of male Wistar rats, hence can be considered potential agent in the management of diabetes-induced oxidative stress male sexual dysfunction.

The Possible Antidiabetic Effects of Ranolazine Versus Gliclazide In HFD/STZ-Induced Type 2 Diabetes In Male Albino Rats

Background: Type 2 diabetes is a major illness that affects millions of people. The key causes of type 2 diabetes are insulin resistance and decreased insulin secretion Objectives: To evaluate the possible effects of ranolazine versus gliclazide on blood glucose levels,HbA1c, nitric oxide and oxidative stress markers in HFD/STZ-induced type 2 diabetes in male albino rats and their effect on the histopathological picture of the pancreas and on apoptosis. Materials and Methods: Thirty-two male albino rats were divided into four groups. The normal control group which received saline (1 mg/kg/day) for 5 weeks. The diabetic control group that received saline (1 mg/kg/day) for 5 weeks. The gliclazide-treated group that received gliclazide (10 mg/kg) twice daily for 5 weeks and the ranolazine-treated group that received ranolazine (20 mg/kg) twice daily for 5 weeks. Body weight and blood glucose levels were measured weekly for the 5 weeks, then blood samples were obtained for various biochemical analysis: lipid profile, HbA1c, AGEs and NO. Then rats were sacrificed and the pancreatic tissues were obtained for oxidative stress markers estimation, for histopathological examination using haematoxylin and eosin stain and for estimation of caspase-3 marker. Results: Ranolazine improved diabetes by reducing fasting blood glucose level, HbA1c, NO and AGEs. Moreover, it improved the oxidative stress markers, the histopathological picture of the pancreas and decreased the apoptosis. Conclusion: Ranolazine has the potential to become a novel agent for treating type 2 diabetes patients.

Bound Phenolics Ensure the Antihyperglycemic Effect of Rice Bran Dietary Fiber in db/db Mice via Activating the Insulin Signaling Pathway in Skeletal Muscle and Altering Gut Microbiota.

Whole-grain dietary fiber intake is beneficial in the prevention of metabolic syndrome. Considering rich in bound phenolics being a special characteristic of whole-grain dietary fiber, the aim of this study was to evaluate the effects of the presence or absence of bound phenolics in rice bran dietary fiber (RBDF) on regulating glucose metabolism in diabetic db/db mice. In comparison to phenolics-removed RBDF (PR-RBDF) intervention without an antihyperglycemic effect, RBDF and formulated RBDF (F-RBDF, obtained by mixing PR-RBDF and hydrolyzed-bound phenolics) significantly reduced fasting blood glucose levels after 1 and 5 weeks of interventions, respectively. The presence of bound phenolics interventions could activate the IRS1/AKT/GLUT4 insulin signaling pathway in skeletal muscle and alter gut microbiota by modulating gut microbiota dysbiosis and enriching the butyric-acid-producing bacteria genera of the families Lachnospiraceae and Ruminococcaceae, thus leading to the reduction of blood glucose levels. These findings indicate that bound phenolics ensure the antihyperglycemic effect of RBDF.

Evaluation of the anti-diabetic effect of the methanol leaf extract and fractions of Dennettia tripetala G. Bak (Annonaceae) in alloxan- induced diabetic mice

This study evaluated the anti-diabetic properties of the methanol extract and fractions of Dennettia tripetala leaves in alloxan diabetic rats. The crude methanol extract (ME), n-hexane (NF), ethyl acetate (EAF), butanol (BF) and water (WF) fractions, were tested for anti-diabetic activity in alloxan-induced diabetic mice. The extracts and its fractions were screened for phytochemical constituents. Glibenclamide was used as the standard anti-diabetic treatment Fasting blood glucose (FBG) levels were determined using a glucometer. Lipid profile parameters were also assessed. Histopathological examination of the pancreas was performed. The presence of glycosides, saponins, reducing sugars, fats and oil, alkaloids, carbohydrates, flavonoids, proteins and tannins were detected in ME, and the fractions. Treatment of the rats with the extract and its fractions reduced FBG levels significantly (p < 0.05) within 10 hours of acute treatment and 14 days short term treatment. The highest reduction was by the crude extract,( ME 500 mg/kg) with percentage reduction of 62.89 %. The study revealed significant (p < 0.05) reductions in serum triglyceride, serum cholesterol and LDL levels by the extracts and its fractions while a significant (p < 0.05) increase in HDL levels was evident . The effect of the extract and fractions on body weight indicated a moderate weight gain. Treatment with high dose of the extract and fractions (500 mg/kg) resulted in marked rejuvenation of the pancreatic β cells. The results of this study suggest that the leaves of Dennetia tripetala are endowed with potent anti-diabetic and antilipidemic properties. 
 Keywords: Dennetia tripetala, Antidiabetic, Alloxan, Lipid profile, Histopathplogy.

Synthesis of selenylated polysaccharides from Momordica charantia L. and its hypoglycemic activity in streptozotocin-induced diabetic mice

In order to obtain the effective antidiabetic polysaccharide derivative, a selenylated polysaccharide (Se-MCPIIa-1), with an average molecular weight (MW) of 4.0038 × 104 Da, was synthesized by reduction of sodium selenite with ascorbic acid in the presence of Momordica polysaccharides (MCPIIa). The selenium (Se) content of Se-MCPIIa-1 was up to 445.0 μg/g, and its average diameter of monodisperse spherical particle size was around 63.78 nm. The morphology and physicochemical properties of Se-MCPIIa-1 were characterized by scanning electron microscope (SEM), atomic force microscope (AFM), Fourier transform infrared spectrometry (FT-IR) and Raman spectroscopy, respectively. The results indicated that Se was conjunct with MCPIIa by esterification. Moreover, the oral administration of Se-MCPIIa-1 showed a gradual normalization in the levels of hypoglyemic test in the STZ-induced diabetic mice. The anti-diabetic effects of Se-MCPIIa-1 in vivo showed that Se-MCPIIa-1 can significantly reduce fasting blood glucose levels and enhance insulin levels as well as antioxidant enzyme activities in diabetic mice with an optimal dosage of 20 mg/kg/body weight. In addition, it was found from histopathological data that Se-MCPIIa-1 could prevent pancreatic islets, liver and kidney damage from diabetes, which suggested that Se-MCPIIa-1 is a promising novel Se supplement and could be applied in the field of food and medicine.

Pengaruh Vitamin D3 Terhadap Glukosa Darah Tikus Wistar Yang Dipapar Asap Rokok

Cigarettes are the biggest health problem around the world. Nicotine in cigarettes has been proved insulin receptor resistance and can reduce insulin secretion in pancreatic β cells, which causes an increase in blood glucose levels. One of the efforts to reduce blood glucose levels is to consume vitamin D3. Vitamin D3 is a prohormone that plays a role in metabolic functions in cells and repair functions of cells. Purpose: to know the effect of vitamin D3 toward glucose blood level of male Rattus norvegicus Wistar exposed by cigarette smoke. Methods: This research conducted with pure experimental pre- and post-test with control group design. The samples used were 24 male rats. The sample divided into four groups, including K1, K2, K3, and P1. K1, which is not exposed by cigarette smoke and not given of vitamin D3. K2 is a group exposed by cigarette smoke but not given vitamin D3. K3 is a group that is not exposed by cigarette smoke but given vitamin D3 a dose of 0.2 µgr /head. P1 is a group exposed by cigarette smoke and given a vitamin D3 dose of 0.2 µgr /head. Results: Paired T-test showed increased blood glucose levels that are meaningful (p<0,05) In groups K2 (p=0,018) and P1 (p=0,035). One-way Anova showed there were differences in blood glucose levels that are meaningful between groups (p=0,001). Statistical analysis Post Hoc LSD showed significant differences in group K1 with K2 (p=0,004), group K1 with K3 (p=0,038), group K1 with P1 (p=0,038), group K2 with K3 (p=0,000), group K2 with P1 (p=0,004). Conclusion: Vitamin D3 can reduce fasting blood glucose levels of Rattus norvegicus exposed by cigarette smoke.

Efficacy and safety of freeze-dried form of Tragia involucrata L. decoction in treating diabetes: a randomized controlled clinical trial

Background and objectives: Tragia involucrata L. (Family: Euphorbiaceae, S. Wel Kahambiliya) is a highly used medicinal plant in both systems of Sri Lankan traditional medicine and Ayurveda medicine. This plant is used for the treatment of diseases such as diabetes, wounds, dysuria, and epilepsy. The aim of this study was to evaluate the efficacy and safety of the freeze-dried form of Tragia involucrata L. decoction in the treatment of diabetes. Subjects and methods: This randomized, two-arm, open-label, controlled clinical trial was conducted in type 2 diabetes patients at National Ayurveda Teaching Hospital in Colombo, Sri Lanka during the year 2016–2017. Thirty-six type 2 diabetes patients aged 18–70 years were included in each group. Patients received treatment with 120 mL of Tragia involucrata L. decoction and 500 mg of metformin, twice a day, for 14 days used as the test drug and positive control drug groups. Fasting blood glucose level was measured on days 0, 8, and 15. Lipid profile and liver and kidney functions were measured on days 0 and 15. This study was approved by the Ethics Review Committee, Institute of Indigenous Medicine (ERCIIM), University of Colombo, Rajagiriya, Sri Lanka (approval No. ERC 16/61) on October 27, 2016.Results: Fasting blood glucose levels in the test group were significantly decreased on days 8 and 15 compared to day 0 (P < 0.05). There was no significant change in the lipid profile values before and after treatment (P > 0.05). Also the decoction did not cause changes in the function of the liver and kidneys. Further no other adverse reactions were recorded in the patients. Conclusion: Tragia involucrata L. can reduce fasting blood glucose level and has antidiabetic effects in diabetes.

Effects of Dioscorea polystachya 'yam gruel' on the cognitive function of diabetic rats with focal cerebral ischemia-reperfusion injury via the gut-brain axis.

Focal cerebral ischemia-reperfusion injury is closely related to hyperglycemia and gut microbiota imbalance, while gut microbiota contributes to the regulation of brain function through the gut-brain axis. Previous studies in patients with diabetes have found that 'yam gruel' is a classic medicated diet made from Dioscorea polystachya, increases the content of Bifidobacterium, regulates oxidative stress, and reduces fasting blood glucose levels. The research reported here investigated the effects of 'yam gruel' on the cognitive function of streptozotocin-induced diabetic rats with focal cerebral ischemia-reperfusion injury and explored the mechanism underlying the role of the gut-brain axis in this process. 'Yam gruel' was shown to improve cognitive function as indicated by increased relative content of probiotic bacteria, and short-chain fatty acids in the intestinal tract and cerebral cortex reduced oxidative stress and inflammatory response and promotion of the expression of neurotransmitters and brain-derived neurotrophic factor. Thus, it is concluded that 'yam gruel' has a protective effect on cognitive function via a mechanism related to the gut-brain axis.

Lack of adipose-specific hexose-6-phosphate dehydrogenase causes inactivation of adipose glucocorticoids and improves metabolic phenotype in mice.

Excessive glucocorticoid (GC) production in adipose tissue promotes the development of visceral obesity and metabolic syndrome (MS). 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) is critical for controlling intracellular GC production, and this process is tightly regulated by hexose-6-phosphate dehydrogenase (H6PDH). To better understand the integrated molecular physiological effects of adipose H6PDH, we created a tissue-specific knockout of the H6PDH gene mouse model in adipocytes (adipocyte-specific conditional knockout of H6PDH (H6PDHAcKO) mice). H6PDHAcKO mice exhibited almost complete absence of H6PDH expression and decreased intra-adipose corticosterone production with a reduction in 11β-HSD1 activity in adipose tissue. These mice also had decreased abdominal fat mass, which was paralleled by decreased adipose lipogenic acetyl-CoA carboxylase (ACC) and ATP-citrate lyase (ACL) gene expression and reduction in their transcription factor C/EBPα mRNA levels. Moreover, H6PDHAcKO mice also had reduced fasting blood glucose levels, increased glucose tolerance, and increased insulin sensitivity. In addition, plasma free fatty acid (FFA) levels were decreased with a concomitant decrease in the expression of lipase adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) in adipose tissue. These results indicate that inactivation of adipocyte H6PDH expression is sufficient to cause intra-adipose GC inactivation that leads to a favorable pattern of metabolic phenotypes. These data suggest that H6PDHAcKO mice may provide a good model for studying the potential contributions of fat-specific H6PDH inhibition to improve the metabolic phenotype in vivo. Our study suggests that suppression or inactivation of H6PDH expression in adipocytes could be an effective intervention for treating obesity and diabetes.

Clinical improvement of diabetes mellitus type 1 by b-D-mannuronic acid (M2000) in a breast cancer patient — as a case report

A 56 years old female with breast cancer (BC) and poor controlled diabetes mellitus type 1 (DM1) which has registered in a clinical trial for assessment of thera­peutic efficacy of b-D-mannuronic acid (M2000) on pre-surgical BC patients is described in this case report. After receiving M2000, the patient was followed for 9 weeks. During this period, cancer mass details, fast­ing blood glucose (FBG) levels, 2-hour post-prandial blood glucose (2HPP), blood uric acid (BUA) level and urine analysis (UA) were continuously controlled. After 9 weeks of treatment with M2000, her FBG, BUA and UA decreased significantly. This finding was exactly in accordance with our published experimental data about the anti-diabetic effect of M2000 in an animal model. Therefore, it might be concluded that M2000 is probably able to improve DM1 by reducing FBG level, BUA level, glycosuria, ketonuria and proteinuria.

Carbon Nanoparticles Inhibit Α-Glucosidase Activity and Induce a Hypoglycemic Effect in Diabetic Mice.

New, improved therapies to reduce blood glucose are required for treating diabetes mellitus (DM). Here, we investigated the use of a new nanomaterial candidate for DM treatment, carbon nanoparticles (CNPs). CNPs were prepared by carbonization using a polysaccharide from Arctium lappa L. root as the carbon source. The chemical structure and morphology of the CNPs were characterized using Fourier-transform infrared spectroscopy, X-ray photoelectron spectroscopy, elemental analysis, and transmission electron microscopy. CNPs were spherical, 10-20 nm in size, consisting of C, H, O, and N, and featuring various functional groups, including C=O, C=C, C–O, and C–N. In vitro, the as-prepared CNPs could inhibit α-glucosidase with an IC50 value of 0.5677 mg/mL, which is close to that of the reference drug acarbose. Moreover, in vivo hypoglycemic assays revealed that the CNPs significantly reduced fasting blood-glucose levels in mice with diabetes induced by high-fat diet and streptozocin, lowering blood glucose after intragastric administration for 42 days. To the best of our knowledge, this is the first report of CNPs exhibiting α-glucosidase inhibition and a hypoglycemic effect in diabetic mice. These findings suggest the therapeutic potential of CNPs for diabetes.

Comparison of glycemic improvement between intermittent calorie restriction and continuous calorie restriction in diabetic mice

BackgroundCalorie restriction (CR) has been well proved to be a powerful tool to improve metabolic health associated with aging; and many types of CR have been proposed. Intermittent CR has become a trend in recent years due to its better compliance than continuous CR every day. However, there are few studies that directly compare the interventional activity of intermittent CR vs continuous CR in metabolic disorders such as diabetes.MethodsIn this study, we analyzed two protocols of intermittent CR with the calorie-matched continuous CR in two diabetic mouse models including db/db and streptozotocin-treated mice. Intermittent CR was carried out by a fasting-mimicking diet (FMD, with 30% calorie intake of the control per day) for 2 days or 5 days (i.e., 2–5 or 5–9 regimes followed by free eating for 5 or 9 days respectively).ResultsIn the two diabetic mouse models, both intermittent CR and continuous CR significantly reduced fasting blood glucose level and improved insulin sensitivity. However, intermittent CR performed significantly better than continuous CR in improving glycemic control and insulin sensitivity in db/db mice. In addition, intermittent CR improved the glucose homeostasis of the db/db mice without causing loss of body weight. Analyses with the pancreatic islets reveal that intermittent CR profoundly elevated the number of insulin-positive cells in both diabetic mouse models.ConclusionsOur study indicated that both intermittent CR and continuous CR can lower fasting blood glucose level in the diabetic mice, while intermittent CR is better than the latter in improving glucose homeostasis in db/db mice.

Trapa natans pericarp extract ameliorates hyperglycemia and hyperlipidemia in type 2 diabetic mice

The pericarp of Trapa natans L., an annual aquatic floating herb belonging to Lythraceae family, is used as a folk medicine in China. In this study, extracts of Trapa natans pericarp were tested both in vitro and in vivo through a high-fat diet with a single medium dosage streptozotocin injection induced type 2 diabetic mice. Different solvent extracts of Trapa natans pericarp showed α-amylase and α-glucosidase inhibitory activity. After four weeks administration, the ethyl acetate extract of Trapa natans pericarp (50 and 100 mg/kg b.w.) reduced fasting blood glucose level, ameliorated oral glucose tolerance and insulin resistance, improved serum lipids alterations in type 2 diabetic mice as well. Additionally, ethyl acetate extract significantly elevated the insulin receptor substrate 1 and Akt serine/threonine kinase phosphorylation compared to diabetic group. HPLC-MS and HPLC-DAD analysis showed that the ethyl acetate extract was rich in hydrolysable tannins. Results support the notion that Trapa natans pericarp extract has a potential hypoglycemic activity.

High-content analysis of constitutive androstane receptor (CAR) translocation identifies mosapride citrate as a CAR agonist that represses gluconeogenesis

The constitutive androstane receptor (CAR) plays an important role in hepatic drug metabolism and detoxification but has recently been projected as a potential drug target for metabolic disorders due to its repression of lipogenesis and gluconeogenesis. Thus, identification of physiologically-relevant CAR modulators has garnered significant interest. Here, we adapted the previously characterized human CAR (hCAR) nuclear translocation assay in human primary hepatocytes (HPH) to a high-content format and screened an FDA-approved drug library containing 978 compounds. Comparison of hCAR nuclear translocation results with the Tox21 hCAR luciferase reporter assay database in 643 shared compounds revealed significant overlap between these two assays, with approximately half of hCAR agonists also mediating nuclear translocation. Further validation of these compounds in HPH and/or using published data from literature demonstrated that hCAR translocation exhibits a higher correlation with the induction of hCAR target genes, such as CYP2B6, than the luciferase assay. In addition, some CAR antagonists which repress CYP2B6 mRNA expression in HPH, such as sorafenib, rimonabant, and CINPA1, were found to translocate hCAR to the nucleus of HPH. Notably, both the translocation assay and the luciferase assay identified mosapride citrate (MOS), a gastroprokinetic agent that is known to reduce fasting blood glucose levels in humans, as a novel hCAR activator. Further studies with MOS in HPH uncovered that MOS can repress the expression of gluconeogenic genes and decrease glucose output from hepatocytes, providing a previously unidentified liver-specific mechanism by which MOS modulates blood glucose levels.

HYPOGLYCEMIC EFFECT OF HIGH-RESISTANT STARCH ANALOG RICE THROUGH GLP-1 AND INSULIN OR HIGH-RESISTANT STARCH ANALOG RICE ATTENUATES BLOOD GLUCOSE LEVEL THROUGH ENHANCEMENT OF GLP-1 AND INSULIN

Objective: This study was to investigate the effect of analog rice (AR) on glucagon-like peptide-1 (GLP-1) and insulin serum levels, glucose transporter-2 (GLUT-2) expression, and fasting blood glucose (FBG) level in diabetic rats.&#x0D; Methods: Fifty male Wistar rats divided into the control group (n=10) and the experimental group. High-fat diet and streptozotocin were administered in experimental groups, which then divided into four equal groups (n=10, each) (negative control group, rice group, AR1 and AR2 group, given standard pellet, rice pellet, AR1 and AR2 pellet, respectively, for 6 weeks). GLP-1 and insulin serum levels were measured by enzyme-linked immunosorbent assay. The expression of GLUT-2 and the number of pancreatic β-cells observed using an immunohistochemistry method.&#x0D; Results: FBG levels in the AR1 and AR2 groups decreased, while the rice group remained. GLP-1 serum levels of the negative control and rice groups were not significantly different from the control group, while the AR1 and AR2 groups higher than the control group (p≤0.05). All the treatment groups had insulin serum levels significantly lower than control group (p≤0.05), except the AR1 group. The expression of GLUT-2 and the number of pancreatic β-cells in the treatment groups were less than the control group, but between treatment groups were not significantly different.&#x0D; Conclusion: AR significantly effective in reducing FBG level in diabetic rats through stimulation of increased GLP-1 and insulin serum levels serum levels but AR did not affect on the expression of GLUT-2.

Effect of heat-killed Streptococcus thermophilus on type 2 diabetes rats.

Background and AimsThe link between gut microbiota and type 2 diabetes (T2D) has been addressed by numerous studies. Streptococcus thermophilus from fermented milk products, has been used as a probiotic in previous research. However, whether heat-killed S. thermophilus can improve the glycemic parameters of diabetic rats remains unanswered. In this study, we evaluated the effect of heat-killed S. thermophilus on T2D model rats and the potential mechanisms of the effect.MethodsZucker diabetic fatty (ZDF) rats were used to generate a diabetic rat model induced by feeding a high-fat diet. Heat-killed S. thermophilus were orally administered to normal and diabetic rats for 12 weeks. Intestinal microbiota analysis, histology analysis, oral glucose tolerance test and measurement of inflammatory factors were performed.ResultsWe found that heat-killed S. thermophilus treatment reduced fasting blood glucose levels and alleviated glucose intolerance and total cholesterol in diabetic ZDF rats. Additionally, heat-killed S. thermophilus increased the interleukin 10 while reducing the levels of lipopolysaccharide, interleukin 6, and tumor necrosis factor-α in diabetic ZDF rats. The heat-killed S. thermophilus treatment can normalize the structure of the intestinal and colon mucosal layer of diabetic rats. The characteristics of the gut microbiota in heat-killed S. thermophilus-treated and control rats were similar. At the genus level, the abundances of beneficial bacteria, including Ruminococcaceae, Veillonella, Coprococcus, and Bamesiella, were all significantly elevated by heat-killed S. thermophilus treatment in ZDF diabetic rats.ConclusionOur study supports the hypothesis that treatment with heat-killed S. thermophilus could effectively improve glycemic parameters in T2D model rats. In addition, the potential mechanisms underlying the protection maybe include changing the composition of gut microbiota, reinforcing the intestinal epithelial barrier and the immunity of the intestinal mucosa, decreasing the level of inflammation, and then reducing the insulin resistance.

2031-P: Adipose-Specific Lack of Hexose-6-Phosphate Dehydrogenase Causes Inactivation of Adipose Glucocorticoids and Improves Metabolic Phenotype in Male Mice

Excessive glucocorticoids (GCs) production in adipose tissue promotes the development of visceral obesity and the metabolic syndrome. 11β-Hydroxysteroid dehydrogenase type 1 (11 β-HSD1) is critical for controlling intracellular GC production in adipose tissue, and this process is also regulated by hexose-6-phosphate dehydrogenase (H6PDH) that provides cofactor NADPH for 11β-HSD1 amplifying local GC production. To better understand the integrated molecular and physiological role of adipose H6PDH, we created a tissue specific knockout of H6PDH gene mouse model in adipocytes (H6PDHAcKO mice) and characterized the metabolic related phenotypes. H6PDHAcKO mice had decreased levels of intra-adipose corticosterone with reduction of 11β-HSD1 activity in response to H6PDH deletion in adipose tissue. Moreover, H6PDHAcKO mice also exhibited reduced fasting blood glucose levels and increased glucose tolerance with increased insulin sensitivity. In addition, plasma FFA levels were decreased with a concomitant decrease in the expression of lipase ATGL and HSL in the abdominal adipose tissue. These results indicate that inactivation of H6PDH expression in adipose tissue is sufficient to cause intra-adipose GC inactivation leading to the favorable pattern of metabolic phenotype. These data suggest that H6PDHAcKO mice may provide a good model for study the potential contributions of fat-specific H6PDH inhibition in the metabolic phenotype and other pathological disorders in vivo. Disclosure J. Wang: None. X. Wang: None. K. Lutfy: None. T. Friedman: None. M. Jiang: None. Y. Liu: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases (SC1DK104821)

143-LB: Calorie Restriction in Combination with GABA Ameliorates Type 2 Diabetes

Dysfunction of adipocytes and β-cells are crucial in the progression of obesity-related insulin resistance and type 2 diabetes (T2D). γ-Aminobutyric Acid (GABA) is a key neurotransmitter and is secreted by β-cells. It exerts protective and regenerative effects on β-cells. At the metabolic level, Calorie Restriction (CR) has been shown to improve insulin sensitivity, reduces Fasting Blood Glucose (FBG) and increases insulin levels. GABA and CR are speculated to show an additive effect on insulin secretion and β-cell regeneration via GABA signaling and enhance insulin sensitivity ameliorating T2D manifestations. We have evaluated the effect of GABA and CR combination on β-cell regeneration and insulin sensitivity in High Fat Diet (HFD) and streptozotocin (STZ) induced late stage T2D mouse model. Our results show favorable changes in the measured parameters. GABA+CR group showed reduced FBG levels and improved whole-body insulin responsiveness indicated by increased insulin levels, insulin sensitivity, and glucose tolerance. The combination therapy improved the lipid profile by significantly reducing triglycerides, total cholesterol, and LDL levels and increased HDL levels. The transcript expression profile of metabolic enzymes in the liver indicates a significant decrease in gluconeogenesis and glycogenolysis. The transcript levels indicate decreased lipolysis and increased fatty acid synthesis in the adipose tissue. The transcript levels of mitochondrial biogenesis in the skeletal muscle indicate increased effect of combination therapy, thereby promoting insulin sensitivity. Also, combination therapy promoted β-cell proliferation. In conclusion, calorie restriction in combination with GABA ameliorates T2D in the mouse model by inducing β-cell regeneration mediated by GABA and increased insulin sensitivity by CR diet. Disclosure N.N. Rathwa: None. R. Patel: None. S. Pramanik: None. N.R. Parmar: None. R. A.v.: None. R. Begum: None. Funding Department of Biotechnology, New Delhi, India (BT/PR21242/MED/30/1750/2016)

Comparison of Glycemic Improvement Between Intermittent Calorie Restriction and Continuous Calorie Restriction in Diabetic Mice

Calorie restriction (CR) has been well proved to be a powerful tool to improve metabolic health associated with aging; and many types of CR have been proposed. Intermittent CR has become a trend in recent years due to its better compliance than continuous CR every day. However, there are few studies that directly compare the interventional efficacy of intermittent CR to continuous CR in metabolic disorders such as diabetes. In this study, we analyzed two regimes of intermittent CR with the calorie-matched continuous CR in two diabetic mouse models including db/db and streptozotocin-treated mice. Intermittent CR was carried out by a fasting-mimicking diet (FMD, with 30% calorie intake of the control per day) for 2 days or 5 days (i.e., 2-5 or 5-9 regimes followed by free eating for 5 or 9 days respectively). In the two diabetic mouse models, both intermittent CR and continuous CR significantly reduced fasting blood glucose level and improved insulin sensitivity. However, intermittent CR performed significantly better than continuous CR in improving glycemic control and insulin sensitivity in db/db mice. In addition, intermittent CR improved the glucose homeostasis of the db/db mice without causing loss of body weight. Analyses with the pancreatic islets reveal that intermittent CR profoundly elevated the number of insulin-positive cells in both diabetic mouse models. In conclusion, our study indicated that both intermittent CR and continuous CR can lower fasting blood glucose level in the diabetic mice, while intermittent CR is better than the latter in improving insulin sensitivity. Funding Statement: This study was supported by research grants from the National Natural Science Foundation of China (31630036 to Y.C.), the Ministry of Science and Technology of China (2016YFA0500103 to Y.C.), and the Chinese Academy of Sciences (XDA12010102, QYZDJ-SSW-SMC008, ZDRW-ZS-2016-8, and Y817X11141 to Y.C Declaration of Interests: The authors declare no conflict of interest. Ethics Approval Statement: The animal experiments were conducted in accordance with the guidelines of the Institutional Animal Care and Use Committee of the Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS) with an approval number 2010-AN-8.