Glucose Homeostasis In Diabetic Rats Research Articles

Garlic Extract Promotes Pancreatic Islet Neogenesis Through α-to-β-Cell Transdifferentiation and Normalizes Glucose Homeostasis in Diabetic Rats.

Garlic extract (GE) has been shown to ameliorate hyperglycemia in diabetic rats (DRs) by increasing insulin production. However, the mechanism through which it exerts its effects remains unclear. Here, it investigates the molecular process and the origin of regenerating β-cell in rats with streptozotocin (STZ)-induced diabetes in response to GE. In this study, quantitative RT-PCR (qRT-PCR), western blotting, and immunohistochemical analysis are carried out after pancreas isolation. These findings show that 1 week of GE treatment increases the expression of the endocrine progenitor cell markers Neurogenin3 (Neurog3), pancreatic and duodenal homeobox 1 (Pdx1), neurogenic differentiation factor 1 (Neurod1), paired box proteins (Pax)4, V-maf musculoaponeurotic fibrosarcoma oncogene homolog B(Mafb),and NK homeobox factors (Nkx)6-1 in STZ-induced DRs. Continuation with GE treatment for 8 weeks causes the expression of the mature β-cell markers insulin(Ins)2, urocortin3 (Ucn3), and glucose transporter 2 (Glut2) to peak. Comprehensive examination of the islet through immunohistochemical analysis reveals the presence of a heterogeneous cell population including INS+/GLUT2- and INS+/GLUT2+ β-cell subpopulations with few bihormonal INS+/GCG+ cells after 4 weeks. By week 8, islet architecture is reestablished, and glucose-stimulated insulin secretion was restored through the upregulation of Ucn3. GE induces β-cell neogenesis in DRs and restores islet architecture. The newly formed mature β-like cells could have originated through the differentiation of endocrine progenitor cells as well as α- to β-cell transdifferentiation.

Comparative impact of streptozotocin on altering normal glucose homeostasis in diabetic rats compared to normoglycemic rats

Diabetes mellitus is a syndrome and an endocrine disorder, primarily considered as a loss of glucose homeostasis because of the insulin action and/or secretion or both. Currently there are more than 150 million people in the world affected by diabetes mellitus with a higher share of Asian and European countries. The current study aimed to investigate the comparative altering properties of streptozotocin (STZ), based on up-turn and down-turn configuration of biochemical, toxicological and hematological parameters in comparison with normoglycemic male albino rats. This comparative study was conducted among normoglycemic and STZ based induced-type 2 diabetic male albino rats groups. The male albino rats were intra-peritoneally injected with STZ with the dose rate of 65 mg/kg body weight for one time to developed type 2 diabetic model. Biochemical (blood glucose, uric acid, urea and creatinine), toxicological (AST, ALT and ALP) and hematological parameters (red and white blood cells) and their functional indices were evaluated in type 2 diabetic induced group along with normoglycemic rats. The STZ based induced- type 2 diabetic rats showed statistically significance (p < 0.001) higher level in the blood glucose, alongwith the change in the levels of biochemical parameters including urea, uric acid, and creatinine. Toxicological parameters comprising AST, ALT and ALP were also shown significance (p < 0.001) as sufficient after experimental evaluation of biologically important parameter in STZ based induced-type 2 diabetic rats. Likewise, the red blood cells, white blood cells and their efficient components were exposed significantly insufficient after the injecting of STZ to induce the rats as type 2 diabetic. The results of the current study indicates the comparatively higher levels of variation among biochemical, toxicological and hematological parameters in STZ based Induced-type 2 diabetic model as compared to normoglycemic group.

Ginger Root Extract Improves GI Health in Diabetic Rats by Improving Intestinal Integrity and Mitochondrial Function.

Background Emerging research suggests hyperglycemia can increase intestinal permeability. Ginger and its bioactive compounds have been reported to benefit diabetic animals due to their anti-inflammatory and antioxidant properties. In this study, we revealed the beneficial effect of gingerol-enriched ginger (GEG) on intestinal health (i.e., barrier function, mitochondrial function, and anti-inflammation) in diabetic rats. Methods Thirty-three male Sprague Dawley rats were assigned to three groups: low-fat diet (control group), high-fat-diet (HFD) + streptozotocin (single low dose 35 mg/kg body weight (BW) after 2 weeks of HFD feeding) (DM group), and HFD + streptozotocin + 0.75% GEG in diet (GEG group) for 42 days. Glucose tolerance tests (GTT) and insulin tolerance tests (ITT) were conducted at baseline and prior to sample collection. Total pancreatic insulin content was determined by ELISA. Total RNA of intestinal tissues was extracted for mRNA expression using qRT-PCR. Results Compared to the DM group, the GEG group had improved glucose tolerance and increased pancreatic insulin content. Compared to those without GEG (DM group), GEG supplementation (GEG group) increased the gene expression of tight junction (Claudin-3) and antioxidant capacity (SOD1), while it decreased the gene expression for mitochondrial fusion (MFN1), fission (FIS1), biogenesis (PGC-1α, TFAM), mitophagy (LC3B, P62, PINK1), and inflammation (NF-κB). Conclusions Ginger root extract improved glucose homeostasis in diabetic rats, in part, via improving intestinal integrity and mitochondrial dysfunction of GI health.

Investigation of FcRn‐Mediated Transepithelial Mechanisms for Oral Nanoparticle Delivery Systems

AbstractOral delivery is the most widely used modality for drug administration, but its efficiency is hampered by the limited drug absorption in the gastrointestinal tract. To address this issue, neonatal‐Fc‐receptor‐targeted liposome (Fc domain‐binding peptide (FcBP)‐Lip) is designed in this study. It is discovered that FcBP modification, by adapting to longitudinal pH gradience of the intestine, increases the unidirectional transport of liposomes from the apical to the basolateral side of the intestinal epithelium. In addition, FcBP‐Lip circumvents the lysosomal sequestration and engages the endoplamic reticulum (ER)–Golgi secretion pathway, together contributing to another mechanism that enhances epithelium transcytosis. Moreover, it is discovered that FcBP‐Lip is subject to paracellular and lymphatic transportations by activating specific intracellular kinases and forming chylomicron, respectively. Owing to the vigorous involvement of the miscellaneous transepithelial transport pathways, oral absorption of FcBP‐Lip in vivo is significantly increased. Finally, the insulin that is encapsulated into FcBP‐Lip elicits a stronger hypoglycemic effect than the native form. Notably, insulin‐loaded FcBP‐Lip efficiently elevates hepatic insulin accumulation, insulin receptor level, and glycogen production, leading to blood glucose homeostasis in diabetic rats.

Native polypeptide vglycin prevents nonalcoholic fatty liver disease in mice by activating the AMPK pathway

• Vglycin ameliorates HFD induced liver injury, inflammation and insulin resistance. • Vglycin prevents HepG2 cells apoptosis from OA induced mitochondrial dysfunction. • Vglycin prevents NAFLD by inhibiting the AMPK mediated liver-fat accumulation. Nonalcoholic fatty liver disease (NAFLD) is one of the most common liver diseases worldwide, and it has no effective treatment. We previously reported that the native polypeptide vglycin (purified from soybean) has a beneficial role in regulating glucose homeostasis in diabetic rats. In this study, we investigated the preventive effects of vglycin and possible mechanisms of action in hepatic steatosis using a high-fat diet (HFD)-induced mouse model. The results revealed that vglycin decreased the body weight, liver weight, Lee’s index, and plasma triglyceride level in HFD-fed C57BL/6J mice. Furthermore, it prevented liver injury, inflammation and insulin resistance by inhibiting fat accumulation in liver. These beneficial effects of vglycin are probably attributable to the activation of the AMP-activated protein kinase (AMPK) pathway and the down-regulation of fatty acid synthase (FAS). Therefore, vglycin holds promise as an oral drug for the prevention of NAFLD.

2010-P: Increasing POMC Positive Neurons and Ameliorating the Brain Inflammation Played an Important Role in DJB Improving Glucose Homeostasis in Diabetic Rats

This study was focused on the effect of duodenal-jejunal bypass (DJB) on brain inflammation, activation brain insulin signaling and POMC positive neurons in type 2 diabetic (T2DM) rats. T2DM rats were induced by high-fat diet (HFD) and low dose streptozotocin (STZ) injection. Twelve T2DM rats were randomly divided into 2 groups, DJB group (T2DM-DJB, n=6) and T2DM group (T2DM-Sham, n=6). Six health Wistar rats were used as normal control rats (Wistar-Control, n=6). The results showed DJB group was significantly reduced the HOMA-IR and increased HOMA-ISI of T2DM rats 6 weeks after surgery. The Q-RT-PCR and Western-blot results showed DJB intervene significantly decreased the expression of inflammatory factors IL-6, TNF-α, IL-1β and NF-κB in the brain. Our data also showed that DJB activated the brain insulin by increasing the expression of insulin, IRS1 and IRS2 in the brain of T2DM rats. Immunohistochemical assay showed that DJB increased the number of POMC positive neurons in brain, and increased the expression of BDNF in neurons. Those results indicated that DJB might fulfill the antidiabetic effect by increasing POMC positive neurons and decreasing the brain inflammation in T2DM rats. Disclosure H. Wang: None. B. Jiang: None. J. Li: None. W. Wang: None. N. Li: None. Q. Yan: None. Z. Gao: None. M. Qu: None. Funding National Natural Science Foundation of China (81871892, 31671208, 81500798, 81471048); Shandong Province Natural Science Foundation (ZR2015HL128); Technology Development Plan of Weifang (2018YX027)

In vivo measurement of the rate constant of liver handling of glucose and glucose uptake by insulin-dependent tissues, using a mathematical model for glucose homeostasis in diabetic rats

Diabetes mellitus is a disease that affects glucose homeostasis. The World Health Organization informs that there are over 347 million people in the world with diabetes. The diagnosis and characterization of glucose homeostasis in different metabolic conditions are subjects of great importance with high clinical impact. There are many mathematical models that describe the glucoregulatory system in detail. However, the use of these models is limited because they have a large number of mathematical equations and parameters and they require complex methodologies to estimate of them. This forced to work with average values that decrease the validity of results and the applicability of the models. In this study two mathematical models for rats with diabetes mellitus were developed. The difference between these models and others lies in the possibility of obtaining all parameters for each animal from simple measurements (glucose and insulin plasma levels). Moreover, the models allow to measure in vivo the different physiological processes involved in glucose homeostasis in animals: insulin secretion and its plasma clearance, absorption of insulin from a subcutaneous injection, the liver handling of glucose, intestine absorption of glucose, glucose uptake rate of insulin-independent tissues, glucose uptake rate of insulin-dependent tissues, and renal glucose excretion.

Amarogentin ameliorates diabetic disorders in animal models.

Amarogentin is a bitter-tasting secoiridoid glycoside isolated from an herb. Inhibition of aldose reductase by amarogentin has been documented as an antidiabetic action. However, the mechanisms of action of amarogentin in diabetic disorders remain unknown. The present study employed streptozotocin-induced type 1 diabetic (T1DM) rats to investigate the antihyperglycemic action of amarogentin. Changes in the protein expression of glucose transporter 4 (GLUT4) and phosphoenolpyruvate carboxykinase (PEPCK) in skeletal muscle and liver, respectively, were also detected by Western blotting. Additionally, a type 2 diabetes (T2DM) animal model induced using a fructose-rich diet was also applied to assess the effect of amarogentin on insulin resistance according to the homeostasis model assessment-insulin resistance (HOMA-IR). Amarogentin dose-dependently attenuated hyperglycemia in the T1DM rats lacking insulin. The action of amarogentin was further supported in rats administered the oral glucose tolerance test. Western blotting showed that amarogentin reversed the decreased GLUT4 level in skeletal muscle and reduced the elevated PEPCK expression in livers isolated from the T1DM rats. Moreover, amarogentin decreased the HOMA-IR and increased insulin sensitivity in the T2DM rats. These data show that amarogentin may ameliorate glucose homeostasis in diabetic rats, indicating its potential for future development as an antidiabetic drug.

Development of PPAR-agonist GW0742 as antidiabetic drug: study in animals.

BackgroundThe development of new drugs for the treatment of diabetes mellitus (DM) is critically important. Insulin resistance (IR) is one of the main problems associated with type-2 DM (T2DM) seen in clinics. GW0742, a selective peroxisome proliferator-activated receptor (PPAR)-δ agonist, has been shown to ameliorate metabolic abnormalities including IR in skeletal muscle in mice fed high-fructose corn syrup. However, the influence of GW0742 on systemic insulin sensitivity has still not been elucidated. Therefore, it is important to investigate the effect of GW0742 on systemic IR in diabetic rats for the development of new drugs.MethodsThe present study used a T2DM animal model to compare the effect of GW0742 on IR using homeostasis model assessment-IR (HOMA-IR) and hyperinsulinemic euglycemic clamping. Additionally, the insulinotropic action of GW0742 was investigated in type-1 DM (T1DM) rats. Changes in the protein expression of glucose transporter 4 (GLUT4) and phosphoenolpyruvate carboxykinase (PEPCK) in skeletal muscle and in liver, respectively, were also identified by Western blots.ResultsGW0742 attenuated the increased HOMA-IR in diabetic rats fed a fructose-rich diet. This action was blocked by GSK0660 at the dose sufficient to inhibit PPAR-δ. Improvement of IR by GW0742 was also characterized in diabetic rats using hyperinsulinemic euglycemic clamping. Additionally, an increase of insulin sensitivity due to GW0742 was observed in these diabetic rats. Moreover, GW0742 reduced the hyperglycemia in T1DM rats lacking insulin. Western blotting analysis indicated that GW0742 reversed the decrease in GLUT4 and markedly reduced the increased PEPCK in liver.ConclusionThe data showed that GW0742 has the ability to improve glucose homeostasis in diabetic rats through activation of PPAR-δ. Therefore, PPAR-δ is a good target for the development of antidiabetic drugs in the future.

Flavanone naringenin: An effective antihyperglycemic and antihyperlipidemic nutraceutical agent on high fat diet fed streptozotocin induced type 2 diabetic rats

Citrus fruits rich in flavonoids elicit their health benefits in prevention/management of metabolic disorders. This study explores the mechanism of naringenin (NG), a flavanone, as an antihyperglycemic and antilipidemic agent on high fat diet (HFD) fed streptozotocin (STZ) induced diabetic rats. NG (25 mg/kg bw) treatment to diabetic rats for 45 days markedly reduced hyperglycemia and hyperinsulinemia, restored lipid profile changes, decreased membrane lipid peroxidation; enhanced the activities of antioxidants and improved hepatic function markers. NG treatment also modulated the expressions of GLUT-4 and TNF-α and restored histological abnormalities in diabetic rats. NG supplementation potentially enhances insulin sensitivity that helps in rebuilding glucose homeostasis in diabetic rats. These findings suggest that NG could be used as a functional and nutraceutical ingredient in combating T2D.

Synthesis, Spectral Characterization, and Biochemical Evaluation of Antidiabetic Properties of a New Zinc-Diosmin Complex Studied in High Fat Diet Fed-Low Dose Streptozotocin Induced Experimental Type 2 Diabetes in Rats.

In view of the established antidiabetic properties of zinc, the present study was aimed at evaluating the hypoglycemic properties of a new zinc-diosmin complex in high fat diet fed-low dose streptozotocin induced experimental type 2 diabetes in rats. Zinc-diosmin complex was synthesized and characterized by various spectral studies. The complexation between zinc ions and diosmin was further evidenced by pH-potentiometric titrations and Job's plot. Diabetic rats were orally treated with zinc-diosmin complex at a concentration of 20 mg/kg b.w./rat/day for 30 days. At the end of the experimental period, the rats were subjected to oral glucose tolerance test. In addition, HOMA-IR and various biochemical parameters related to glucose homeostasis were analyzed. Treatment with zinc-diosmin complex significantly improved the glucose homeostasis in diabetic rats. Treatment with zinc-diosmin complex significantly improved insulin sensitivity, at least in part, through enhancing protein metabolism and alteration in the levels of muscle and liver glycogen. The assay of clinical marker enzymes revealed the nontoxic nature of the complex. Determination of renal tissue markers such as blood urea and serum creatinine indicates the renoprotective nature of the complex. These findings suggest that zinc-diosmin complex is nontoxic and has complimentary potential to develop as an antihyperglycemic agent for the treatment of diabetes mellitus.

β-Caryophyllene, a natural sesquiterpene, modulates carbohydrate metabolism in streptozotocin-induced diabetic rats

The study was designed to evaluate the antihyperglycemic effects of β-caryophyllene (BCP), a natural sesquiterpene from spices on streptozotocin (STZ) induced diabetic rats. Diabetes mellitus was induced by a single intraperitoneal injection of STZ (40mg/kg b.w.) in adult male Wistar rats. Diabetic rats exhibited an increase in glucose and HbA1c with a significant fall in insulin and hemoglobin levels. Aberrations in carbohydrate metabolic enzymes were noticed in liver, kidney and skeletal muscle of diabetic rats. A fall in liver and skeletal muscle glycogen with alterations in glycogen synthase and phosphorylase activities was also observed. Oral administration of BCP in dose dependent manner and glibenclamide (600μg/kg b.w.), a standard oral hypoglycemic drug to diabetic rats for 45 days significantly decreased glucose with increased plasma insulin levels and ameliorated the altered activities of carbohydrate metabolic enzymes to near normal. The insulinotropic effect of BCP was supported by immunohistochemical studies. BCP at a dose of 200mg/kg b.w. exerted significant antidiabetic effects than other two doses (100 and 400mg/kg b.w.). We conclude that administration of BCP has beneficial effects in glucose homeostasis in diabetic rats.

Co-administration of paroxetine and pravastatin causes deregulation of glucose homeostasis in diabetic rats via enhanced paroxetine exposure.

Clinical evidence shows that co-administration of pravastatin and paroxetine deregulates glucose homeostasis in diabetic patients. The aim of this study was to verify this phenomenon in diabetic rats and to elucidate the underlying mechanisms. Diabetes mellitus was induced in male SD rats by a high-fat diet combined with a low-dose streptozotocin injection. The rats were orally administered paroxetine (10 mg/kg) and pravastatin (10 mg/d) or both the drugs daily for 28 d. The pharmacokinetics of paroxetine and pravastatin were examined on d 1 and d 28. Biochemical parameters including serum insulin, glucose and lipids were monitored during the treatments. An insulin-secreting cell line (INS-1) was used for measuring insulin secretion. In diabetic rats, co-administration of paroxetine and pravastatin markedly increased the concentrations of both the drugs compared with administration of each drug alone. Furthermore, co-administration severely impaired glucose homeostasis in diabetic rats, as demonstrated by significantly increased serum glucose level, decreased serum and pancreatic insulin levels, and decreased pancreatic Insulin-2 mRNA and tryptophan hydroxylase-1 (Tph-1) mRNA levels. Treatment of INS-1 cells with paroxetine (5 and 10 μmol/L) significantly inhibited insulin secretion, decreased the intracellular insulin, 5-HT, Insulin-2 mRNA and Tph-1 mRNA levels. Treatment of the cells with pravastatin (10 μmol/L) significantly stimulated insulin secretion, which was weakened by co-treatment with paroxetine. Paroxetine inhibits insulin secretion at least via decreasing intracellular 5-HT and insulin biosynthesis. The deregulation of glucose homeostasis by co-administration of paroxetine and pravastatin in diabetic rats can be attributed to enhanced paroxetine exposure.

Mid to Distal Small Bowel Resection with the Preservation of the Terminal Ileum Improves Glucose Homeostasis in Diabetic Rats by Activating the Hindgut-Dependent Mechanism

BackgroundThe aim of this study was to develop a novel surgical model to test the “hindgut hypothesis” and thereby study the role of the gut in glucose homeostasis and the mechanism of action of bariatric surgery. MethodSprague-Dawley rats were given a high-fat and high-sugar diet and treated with 25 mg/kg streptozotocin (STZ). The fat-sugar-fed/STZ-treated rats were randomized into mid to distal small bowel resection with the preservation of the terminal ileum (DBRPI) and sham operation (which had a formal celiotomy with bowel manipulation only) groups. Rats were observed for 12 weeks after the operation. The main outcome measures were weight, food intake, non-fasting glucose, an oral glucose tolerance test (OGTT), an insulin tolerance test (ITT), the levels of fasting and glucose-induced insulin, glucagon-like peptide-1 (GLP-1), peptide YY (PYY), serum bile acids, and lipid profile. ResultThe DBRPI and sham groups exhibited no difference in weight and food intake after surgery. When compared to the sham controls, the DBRPI group displayed an improvement in non-fasting glucose, oral glucose tolerance, and insulin tolerance at 4 and 12 weeks postresection. DBRPI elicited an increased serum insulin, PYY and GLP-1 levels at 12 weeks postoperation; furthermore, DBRPI resulted in higher serum levels of triglyceride, total bile acids, total bilirubin, and direct bilirubin levels and lower free fatty acid level at 12 weeks. ConclusionsThis study provides strong evidences for the key role of hindgut in the amelioration of diabetes after bariatric surgery. Moreover, these findings confirm that DBRPI is a simple and effective surgical model for testing the “hindgut hypothesis” and focused study of biliary enterohepatic recycling in the context of bariatric operations.

Islet Transplantation in a Subarachnoid Cavity Surrounding Olfactory Bulb of Diabetic Rats

Islet Transplantation in a Subarachnoid Cavity Surrounding Olfactory Bulb of Diabetic Rats

Traditional Medicine in Management of Type 2 Diabetes Mellitus

The incidence of type 2 diabetes mellitus has now reached epidemic proportions. Although the disease manifests in the form of hyperglycemia, the cause could be varied ranging from disturbance in insulin secretion, insulin action, insulin resistance, glucose production and glucose uptake, interplay between different hormones, and various kind of stress. Due to such varied etiology, the management of diabetic condition poses a great medical challenge. No single agent has so far been unequivocally accepted as the antidiabetic drug. Alternative systems of medicine based on traditional wisdom have thrived through ages and are still practiced by a large population for the management of diabetes. A large number of plants have proved their efficacy in management of diabetes especially hyperglycemia. In many cases, scientific studies have validated the antidiabetic nature of plant-based medicines, and the bioactive principle has been isolated and characterized. It is important that more research is done to understand the mechanism(s) involved in the antidiabetic action of large number of plant-based medicines used as traditional therapy for the management of diabetic condition. The present special volume has brought together some interesting papers reporting the findings of the use of traditional medicines for the treatment of diabetes mellitus. S. I. Rizvi and N. Mishra provide a good review of the anti-diabetic potential and the bioactive compounds present in Ficus religiosa, Pterocarpus marsupium, Gymnema sylvestre, Allium sativum, Eugenia jambolana, Momordica charantia, and Trigonella foenum-graecum. All these plants are widely used in the Indian subcontinent for the management of diabetic condition. O. Eleazu et al. explore the chemical composition of cocoyam and unripe plantain flours and their potential in the dietary prevention of diabetic complications. D. Bailbe and colleagues evaluate the effects of Subetta (containing release-active dilutions of antibodies to beta-subunit of insulin receptor and antibodies to endothelial nitric oxide synthase) in Goto Kakizaki diabetic rats and demonstrate that 28-day administration improves glucose control to an extent similar to that of Rosiglitazone. H. Y. Jin et al. have tested the efficacy of DA-9801, a mixture of extracts from Dioscorea japonica and Dioscorea nipponica in the treatment of diabetic peripheral neuropathy in experimental diabetes. They have also presented a comparison of the effect of DA-9801 with lipoic acid. Statins are very widely used during dyslipidemia. Since type 2 diabetes is frequently associated with dyslipidemia, it is important to investigate the effect of statins on glucose homeostasis in diabetes. Wang et al. report that simvastatin may cause hyperglycemia and have an adverse effect on glucose homeostasis in diabetic rats. Syed Ibrahim Rizvi Elena Matteucci Pinar Atukeren

Effects of Exercise on AMPK Signaling and Downstream Components to PI3K in Rat with Type 2 Diabetes

Exercise can increase skeletal muscle sensitivity to insulin, improve insulin resistance and regulate glucose homeostasis in rat models of type 2 diabetes. However, the potential mechanism remains poorly understood. In this study, we established a male Sprague–Dawley rat model of type 2 diabetes, with insulin resistance and β cell dysfunction, which was induced by a high-fat diet and low-dose streptozotocin to replicate the pathogenesis and metabolic characteristics of type 2 diabetes in humans. We also investigated the possible mechanism by which chronic and acute exercise improves metabolism, and the phosphorylation and expression of components of AMP-activated protein kinase (AMPK) and downstream components of phosphatidylinositol 3-kinase (PI3K) signaling pathways in the soleus. As a result, blood glucose, triglyceride, total cholesterol, and free fatty acid were significantly increased, whereas insulin level progressively declined in diabetic rats. Interestingly, chronic and acute exercise reduced blood glucose, increased phosphorylation and expression of AMPKα1/2 and the isoforms AMPKα1 and AMPKα2, and decreased phosphorylation and expression of AMPK substrate, acetyl CoA carboxylase (ACC). Chronic exercise upregulated phosphorylation and expression of AMPK upstream kinase, LKB1. But acute exercise only increased LKB1 expression. In particular, exercise reversed the changes in protein kinase C (PKC)ζ/λ phosphorylation, and PKCζ phosphorylation and expression. Additionally, exercise also increased protein kinase B (PKB)/Akt1, Akt2 and GLUT4 expression, but AS160 protein expression was unchanged. Chronic exercise elevated Akt (Thr308) and (Ser473) and AS160 phosphorylation. Finally, we found that exercise increased peroxisome proliferator-activated receptor-γ coactivator 1 (PGC1) mRNA expression in the soleus of diabetic rats. These results indicate that both chronic and acute exercise influence the phosphorylation and expression of components of the AMPK and downstream to PIK3 (aPKC, Akt), and improve GLUT4 trafficking in skeletal muscle. These data help explain the mechanism how exercise regulates glucose homeostasis in diabetic rats.

Consumption of Helianthus tuberosus Linne and chungkookjang have additive anti‐diabetic effects in diabetic rats

Helianthus tuberosus Linne (HTL) rich in fructoligosaccarides and chungkookjang (CKJ; fermented soybeans) containing isoflavonoid aglycones and small peptides is known to modulate glucose metabolism. However, the action mechanism and their additive effects were not determined. We investigated whether the consumption of HTL and CKJ alters glucose homeostasis in type 2 diabetic rats. The 90% pancreatectomized (Px) diabetic rats were provided with high fat diets containing 10% HTL, CKJ or HTL+CKJ for 8 weeks. None of the Px rat groups experienced changes in body weight but HTL reduced visceral fat without modulating caloric intake, compared to the control. Both HTL and CKJ improved glucose tolerance compared to the control and HTL+CKJ resulted in additive effects. HTL alleviated hepatic insulin resistance better than CKJ during the euglycemic hyperinsulinemic clamp. The improvement in hepatic insulin sensitivity by HTL and CKJ was explained by the potentiated insulin signaling (pyIRS2→pAkt) and pAMPK→pACC and decreased PEPCK expression. HTL reduced hepatic glucose output. CKJ potentiated glucose‐stimulated insulin secretion better than HTL during hyperglycemic clamp. HTL decreased β‐cell apoptosis, but not proliferation, compared to the control and HTL did not increase β‐cell mass as much as CKJ. In conclusion, the combination of HTL and CKJ additively improves glucose homeostasis in diabetic rats.

Spirulina, exercício e controle da glicemia em ratos diabéticos

The objective of this study was to analyze the effect of Spirulina and/or exercise training in the control of serum glucose homeostasis in diabetic rats. Young Wistar rats were induced to diabetes by intravenous alloxan administration and separated into four groups: diabetic control (DC), diabetic Spirulina (DS), diabetic exercise (DE) and diabetic exercise Spirulina (DES). There were no differences between groups with respect to: body weight, food intake, glucose tolerance, insulin tolerance and blood lactate concentrations during a swimming effort test. DS group showed lower insulin concentrations when compared with DC (pancreas) and DE and DES (serum). The protocols of exercise and supplementation with Spirulina used in the present study were not able to improve serum glucose homeostasis in diabetic rats.

A novel long acting DPP-IV inhibitor PKF-275-055 stimulates β-cell proliferation resulting in improved glucose homeostasis in diabetic rats

The enzyme dipeptidyl peptidase-IV (DPP-4) inactivates the incretin hormone glucagon-like peptide-1 (GLP-1). GLP-1 has therapeutic effects in patients with type 2 diabetes, but its potential is limited by a short half-life, DPP-4 inhibition is a promising approach to diabetes treatment. This study examined chronic (once-a-day dosing for 8 weeks) effects of the DPP-4 inhibitor PKF-275-055 (1, 3, and 10 mg/kg) on β-cell regeneration and plasma DPP-IV activity, intact GLP-1, glucose, and insulin after an oral glucose load in neonatal wistar rats injected with streptozotocin (STZ) (n2-STZ model), a recognized model of type 2 diabetes. In streptozotocin induced diabetic rats, PKF-275-055 (3, and 10 mg/kg) significantly reduced glucose excursion during the oral glucose tolerance test conducted 2 h and 10 h after administration, with increases in plasma insulin and active glucagon-like peptide-1 (GLP-1) levels and significantly inhibited (> 50% inhibition) plasma DPP-IV activity during both the 1st and 2nd OGTT in diabetic rats. In contrast, PKF-275-055 (1–10 mg/kg) did not cause hypoglycemia in fasted normal rats. Furthermore, PKF-275-055 significantly inhibited advance glycation end product (HbA1c), HOMA-Index, gastric emptying and small intestinal transit rates, with significance at doses of 1 mg/kg or higher. Immunological staining showed PKF-275-055 stimulates β-cell regeneration and reduces pancreatic cell apoptosis in diabetic treated rats. The present preclinical studies indicate that PKF-275-055 is a novel selective DPP-IV inhibitor with long-acting antidiabetic effect that might be a potential agent for type 2 diabetes