Non-obese Type Research Articles

Cinnamic acid exerts anti-diabetic activity by improving glucose tolerance in vivo and by stimulating insulin secretion in vitro

Although the anti-diabetic activity of cinnamic acid, a pure compound from cinnamon, has been reported but its mechanism(s) is not yet clear. The present study was designed to explore the possible mechanism(s) of anti-diabetic activity of cinnamic acid in in vitro and in vivo non-obese type 2 diabetic rats. Non-obese type 2 diabetes was developed by injecting 90 mg/kg streptozotocin in 2-day-old Wistar pups. Cinnamic acid and cinnamaldehyde were administered orally to diabetic rats for assessing acute blood glucose lowering effect and improvement of glucose tolerance. Additionally, insulin secretory activity of cinnamic acid and cinnamaldehyde was evaluated in isolated mice islets. Cinnamic acid, but not cinnamaldehyde, decreased blood glucose levels in diabetic rats in a time- and dose-dependent manner. Oral administration of cinnamic acid with 5 and 10 mg/kg doses to diabetic rats improved glucose tolerance in a dose-dependent manner. The improvement by 10 mg/kg cinnamic acid was comparable to that of standard drug glibenclamide (5 mg/kg). Further in vitro studies showed that cinnamaldehyde has little or no effect on glucose-stimulated insulin secretion; however, cinnamic acid significantly enhanced glucose-stimulated insulin secretion in isolated islets. In conclusion, it can be said that cinnamic acid exerts anti-diabetic activity by improving glucose tolerance in vivo and stimulating insulin secretion in vitro.

Differences in emotional distress among inpatients with type 1, obese type 2, and non-obese type 2 diabetes mellitus.

Objective The purpose of this study was to determine the differences in emotional distress among three groups of inpatients with type 1, obese type 2, and non-obese type 2 diabetes during hospitalization. Methods The 42 participating inpatients were divided into three groups: type 1 diabetes (n=11), obese type 2 diabetes [body mass index (BMI) ≥25 kg/m(2); n=24], and non-obese type 2 diabetes (BMI <25 kg/m(2); n=7). The Problem Areas in Diabetes (PAID) scale, which is a self-administered questionnaire to assess emotional distress in the patients with diabetes, was performed at admission and discharge. Results The total PAID score was similar and tended to improve during hospitalization in all three groups, although there were differences among the groups in the scores of particular questions. At admission, the score of the question "worrying about low blood sugar reactions?" was significantly different among the three groups and highest in the patients with type 1 diabetes. At discharge, the score of "not accepting diabetes?" was significantly different among the three groups and highest in the patients with non-obese type 2 diabetes, while that of "feeling unsatisfied with your diabetes physician?" was significantly different among the three groups and highest in the patients with obese type 2 diabetes. The score of "feelings of deprivation regarding food and meals?" significantly worsened in the patients with obese type 2 diabetes during hospitalization compared with the patients in with non-obese type 2 diabetes. Conclusion The characteristics of emotional distress during hospitalization varied among the patients with the three types of diabetes, thus emphasizing the importance of tailoring support according to the type of diabetes.

A comparative study of epicardial fat thickness and its association with abdominal visceral fat thickness in obese and nonobese type 2 diabetes subjects

Context:The concept of visceral fat and its role in various metabolic disorders is well-known. Epicardial fat (EF) is also visceral fat, and very few studies are done, especially in the Indian subcontinent.Aims:To study and establish the relationship of EF thickness (EFT) and abdominal visceral fat thickness (VAT) in obese and nonobese type 2 diabetics and to evaluate the usefulness of EFT as a marker of visceral adiposity.Settings and Designs:This cross-sectional study was carried out in the Department of Medicine, JSS Hospital, Mysore, India, between October 2012 and October 2014.Materials and Methods:A total of 68 patients were studied. Patients underwent transthoracic echocardiography and ultrasound abdomen. EFT and VAT were measured.Statistical Analysis:SPSS version 17.0 (SPSS Inc., Chicago, IL, USA) was used. T-test used for comparing quantitative variables. Correlation analysis was done using Pearson correlation test. P ≤ 0.05 was considered statistically significant. Kruskal-Wallis and Mann-Whitney test were used for analysis.Results:The mean value of EFT was 5.92 mm, 7.43 mm, 12.97 mm, 11.27 mm, and 13.8 mm for nonobese, obesity Grade I, II, III, and morbid, respectively (P < 0.0001). The mean EFT between nonobese and obese diabetics was 5.92 mm and 10.2 mm, respectively (P < 0.0001). The mean VAT between nonobese and obese diabetics was 16.58 mm and 38.53 mm, respectively. EFT was significantly correlating with VAT in obese diabetics.Conclusion:EFT and VAT were significantly correlated among obese diabetics while not significantly correlated among nonobese diabetics, suggesting obesity is an independent risk factor for visceral adipose tissue deposition both in abdomen as well as in epicardial surface.

Immunohistochemical Evidence of Pancreatic beta-cell Regeneration in streptozotocin-induced type 2 Diabetic Rats treated with Gymnema sylvestre Extract

The effective dose Gymnema sylvestre (GS) leaves methanolic extract (400 mg/kg) was administered orally to neonatally streptozotocin-induced non-obese type 2 diabetic rats for 28 days and fasting glucose, serum insulin and β-cell function were measured after the treatment periods. Pancreatic β- and α-cells were identified by immunohistochemistry and β-cells number was evaluated by morphometric analysis. GS extract showed antidiabetic activity through improving serum insulin and β-cell function. The β-cells number was increased significantly in the GS-treated diabetic rats. The immunohistochemal data revealed presence of few newly formed insulin positive β-cells in the GS-treated diabetic islets. This is the direct immunohistochemal evidence of β-cells regeneration and/ or neoformation in pancreatic islets by GS extract. Cluster of β-cells without any α-cells were appeared in GS-treated diabetic rats, not in STZ-induced diabetic control rats, suggesting β-cells regeneration in GS-treated pancreas rather than stem-cell induced growth.

Inhibitory effect of black tea and its combination with acarbose on small intestinal α-glucosidase activity

Ethnopharmacological relevanceIt is said that black tea is effective against type 2 diabetes mellitus because it can help modulate postprandial hyperglycemia. However, the mechanism underlying its therapeutic and preventive effects on type 2 diabetes mellitus is unclear. In this study, we focused on the effect of black tea on the carbohydrate digestion and absorption process in the gastrointestinal tract. We examined whether black tea can modulate postprandial hyperglycemia. Materials and methodsThe freeze-dried powder of the aqueous extract of black tea leaves (JAT) was used for in vitro studies of α-amylase activity, α-glucosidase activity, and glucose uptake by glucose transporters in Caco-2 cells; ex vivo studies of small intestinal α-glucosidase activity; and in vivo studies of oral sugar tolerance in GK rats, an animal model of nonobese type 2 diabetes mellitus. ResultsHalf maximal inhibitory concentration values indicated that JAT significantly reduced α-glucosidase activity, but weakly reduced α-amylase activity. Kinetic studies of rat small intestinal α-glucosidase activity revealed that the combination of JAT and the α-glucosidase inhibitor, acarbose, showed a mixed-type inhibition. JAT had no effect on the uptake of 2′-deoxy-d-glucose by glucose transporter 2 (GLUT2) and the uptake of α-methyl-d-glucose by sodium-dependent glucose transporter 1 (SGLT1). In the oral sucrose tolerance test in GK rats, JAT reduced plasma glucose levels in a dose-dependent manner compared with the control group. The hypoglycemic action of JAT was also confirmed: JAT, in combination with acarbose, produced a synergistic inhibitory effect on plasma glucose levels in vivo. In contrast to the oral sucrose tolerance test, JAT showed no effect in the oral glucose tolerance test. ConclusionsJAT was demonstrated to inhibit the degradation of disaccharides into monosaccharides by α-glucosidase in the small intestine. Thereby indirectly preventing the absorption of the dietary source of glucose mediated by SGLT1 and GLUT2 transporters localized at the apical side of enterocytes in the small intestine. The results indicate that black tea could be useful as a functional food in the dietary therapy for borderline type 2 diabetes mellitus that could modulate postprandial hyperglycemia.

Lipid Peroxidation and Antioxidant Status in Nonobese Type 2 Diabetes Mellitus

The aim of the study was to investigate the association between lipid peroxidation and antioxidant status in nonobese type 2 diabetes mellitus (T2DM) and further to correlate whether their significant association is putatively associated with the pathogenesis of T2DM. A number of 102 nonobese T2DM subjects and 95 nondiabetic subjects as healthy controls were enrolled in this cross-sectional study. Serum samples were collected in cryovials for malondialdehyde (MDA) and thiol assays. Total thiol or sulfhydryl (–SH) groups in peripheral blood mononuclear cells (PBMCs) and sera, as well as level of MDA, a marker for lipid peroxidation in serum, were measured spectrophotometrically. Serum MDA level was found significantly higher whereas serum and PBMC total thiol levels were diminished significantly among nonobese T2DM subjects compared to HC subjects. Moreover, serum MDA level is found to have a significant inverse correlation with serum total thiol and PBMC thiol levels among DM subjects, but no significant correlation was observed in HC individuals. A significant inverse correlation between serum MDA and serum total thiol levels among nonobese T2DM subjects suggests a close association of increased oxidative stress with decreased antioxidant status in nonobese T2DM.

Enhanced ROS production and oxidative damage in subcutaneous white adipose tissue mitochondria in obese and type 2 diabetes subjects.

Oxidative stress in the insulin target tissues has been implicated in the pathophysiology of type 2 diabetes. The study has examined the oxidative stress parameters in the mitochondria of subcutaneous white adipose tissue from obese and non-obese subjects with or without type 2 diabetes. An accumulation of protein carbonyls, fluorescent lipid peroxidation products, and malondialdehyde occurs in the adipose tissue mitochondria of obese type 2 diabetic, non-diabetic obese, and non-obese diabetic subjects with the maximum increase noticed in the obese type 2 diabetes patients and the minimum in non-obese type 2 diabetics. The mitochondria from obese type 2 diabetics, non-diabetic obese, and non-obese type 2 diabetics also produce significantly more reactive oxygen species (ROS) in vitro compared to those of controls, and apparently the mitochondrial ROS production rate in each group is proportional to the respective load of oxidative damage markers. Likewise, the mitochondrial antioxidant enzymes like superoxide dismutase and glutathione peroxidase show decreased activities most markedly in obese type 2 diabetes subjects and to a lesser degree in non-obese type 2 diabetes or non-diabetic obese subjects in comparison to control. The results imply that mitochondrial dysfunction with enhanced ROS production may contribute to the metabolic abnormality of adipose tissue in obesity and diabetes.

Association of adipokines, leptin/adiponectin ratio and C-reactive protein with obesity and type 2 diabetes mellitus.

ObjectiveAlterations in plasma adipokines and/or inflammatory parameters in Type 2 DM remain vague as to whether they are due to obesity and/or directly associated with the diabetic state. Our objective was to compare plasma adiponectin, leptin, leptin/adiponectin ratio (LAR) and hs-CRP in obese non-diabetic subjects and non-obese Type 2 DM patients, as well as determining the association of these adipokines with MetS and diabetes-related quantitative traits.MethodsIn this study, 92 Yemeni male volunteers aged 25–60 years old were enrolled, 31 of whom were healthy subjects with BMI < 25 kg/m2 served as control; 30 non-diabetic obese subjects BMI ≥ 30 kg/m2 and FBG < 6.1 mmol/l; and 31 non-obese Type 2 DM with FBG > 7 mmol/l and BMI < 25 kg/m2.ResultsAdiponectin was lower in obese subjects, with no differences between non-obese Type 2 DM patients and controls. In contrast, leptin, LAR and hs-CRP were higher in both obese subjects and non-obese Type 2 DM patients. Linear regression analysis showed adiponectin to be associated negatively with BMI, waist circumference, insulin, HOMA-β and HOMA-IR; whereas leptin, LAR and hs-CRP were associated positively with BMI, waist circumference, TG, FBG, insulin, HOMA-β and HOMA-IR. Moreover, adiponectin negatively correlated with leptin, LAR and hs-CRP; whereas leptin and LAR positively correlated with hs-CRP and with each other.ConclusionPlasma adiponectin is not affected by diabetes per se, suggesting that its alterations in Type 2 DM may be due to obesity and may be an important link between adiposity, IR and Type 2 DM.

Bisphosphonate-related osteonecrosis of the jaws in a spontaneously diabetic Torii rat model

Bisphosphonates (BPs) are a widely used class of drugs that are effective in the treatment and prevention of hypercalcemia of malignancy and skeletal events associated with multiple myeloma, bone metastasis from cancer, and osteoporosis. However, reports of BP-related osteonecrosis of the jaws (BRONJ) have generated a great concern regarding the safety of these drugs. Some reports in the literature have documented a few animal models with risk factors contributing to the development of BRONJ. Diabetes mellitus is one of the systemic risk factors for this condition. We evaluated the side effects of BPs on extraction socket healing in spontaneously diabetic Torii (SDT) rats, which is an established model of non-obese type 2 diabetes mellitus.

Plasma thrombin-activatable fibrinolysis inhibitor levels in children and adolescents with type 1 diabetes mellitus

Thrombin-activatable fibrinolysis inhibitor (TAFI) is a potent inhibitor of fibrinolysis isolated from human plasma. This study was designed to investigate the association between TAFI levels in relation to metabolic control, microvascular complications and lipid profile in a cohort of Egyptian children and adolescents with type 1 diabetes mellitus (T1DM). Eighty normotensive nonobese type 1 diabetic patients (45 with and 35 without microvascular complications) with a mean age of 12.75 ± 3.6 years and mean disease duration of 7.42 ± 2.4 years in addition to 60 sex and age-matched normal individuals were enrolled in this study. Anthropometric measurements, blood pressure and microvascular complications were analysed. HbA1c, albumin-to-creatinine ratio in urine, lipid profile and TAFI levels were measured. Plasma level of TAFI in diabetic patients was significantly elevated, compared with normal individuals (16 ± 2.8 vs. 10.3 ± 0.7 μg/ml; P < 0.004). Plasma level of TAFI in diabetic patients with microvascular complications was significantly higher than in diabetic patients without complications (17.9 ± 1.8 vs. 12.9 ± 0.6 μg/ml; P < 0.001). Plasma TAFI levels were positively correlated with HbA1c levels (r = 0.38; P < 0.03) and SBP (r = 0.37; P < 0.02). Total cholesterol and triglycerides were higher in patients with microvascular complications than in those without complications (P < 0.001, P < 0.05, respectively). Our results showed that TAFI is considered a valid predictor for microvascular complications with best cut off value 15 μg/ml with sensitivity of 99% and specificity of 100%. Our data imply that increased plasma TAFI as well as high lipid levels may be involved in the mechanism of vascular endothelial damage in patients with T1DM. This suggests the possibility of TAFI participating in the mechanism of hypofibrinolysis, hence occurrence of microvascular complications in diabetes.

Clinical features of fatty liver in nonobese Japanese without regular alcohol intake

The clinical features of fatty liver (FL) detected by ultrasonography (US) in nonobese and diabetes mellitus type 2 are not yet understood, and metabolic syndrome (MetS) has become an important health issue throughout the world. We investigated the clinical features of fatty liver (FL) in nonobese patients. From 2008 to 2010, 2192 Japanese patients underwent a medical checkup at our hospital. Obesity was defined as a body mass index (BMI) ≥25 kg/m2, while normal waist circumference (WC) was defined as <85 cm in males and <90 cm in females. FL was determined in 958 after excluding subjects who regularly drank alcohol (≥20 g/day), who were obese, or had an abnormal WC. We evaluated the clinical backgrounds [biological and lipid examination results, fasting blood sugar, hemoglobin A1c, insulin, HOMA-R, blood pressure (BP), BMI, and medical interviews]. BP, triglyceride, and HOMA-R levels were significantly elevated in nonobese with normal WC with FL (males: 122/78 vs. 120/76 mmHg, 161.5 vs. 105.5 mg/dl, 1.9 vs. 1.3, respectively; females: 120/73 vs. 116/71 mmHg, 115.2 vs. 82.0 mg/dl, 1.7 vs. 1.3, respectively). Both males and females with FL had a past history of increased body weight over 10 kg after reaching the age of 20 years as compared to those without FL (P < 0.01 and P = 0.04, respectively). Nonobese subjects with normal WC and FL had significantly higher BP, triglyceride, and HOMA-R levels than nonobese subjects with normal WC without FL. Lifestyle instruction should be given to such individuals to prevent insulin resistance and progression to MetS.

Mitochondrial quality control systems sustain brain mitochondrial bioenergetics in early stages of type 2 diabetes.

Mitochondria have a crucial role in the supply of energy to the brain. Mitochondrial alterations can lead to detrimental consequences on the function of brain cells and are thought to have a pivotal role in the pathogenesis of several neurologic disorders. This study was aimed to evaluate mitochondrial function, fusion-fission and biogenesis and autophagy in brain cortex of 6-month-old Goto-Kakizaki (GK) rats, an animal model of nonobese type 2 diabetes (T2D). No statistically significant alterations were observed in mitochondrial respiratory chain and oxidative phosphorylation system. A significant decrease in the protein levels of OPA1, a protein that facilitates mitochondrial fusion, was observed in brain cortex of GK rats. Furthermore, a significant decrease in the protein levels of LC3-II and a significant increase in protein levels of mTOR phosphorylated at serine residue 2448 were observed in GK rats suggesting a suppression of autophagy in diabetic brain cortex. No significant alterations were observed in the parameters related to mitochondrial biogenesis. Altogether, these results demonstrate that during the early stages of T2D, brain mitochondrial function is maintained in part due to a delicate balance between mitochondrial fusion-fission and biogenesis and autophagy. However, future studies are warranted to evaluate the role of mitochondrial quality control pathways in late stages of T2D.

Automated image analysis of a glomerular injury marker desmin in spontaneously diabetic Torii rats treated with losartan.

Diabetic nephropathy is a major complication in diabetes and a leading cause of end-stage renal failure. Glomerular podocytes are functionally and structurally injured early in diabetic nephropathy. A non-obese type 2 diabetes model, the spontaneously diabetic Torii (SDT) rat, is of increasing preclinical interest because of its pathophysiological similarities to human type 2 diabetic complications including diabetic nephropathy. However, podocyte injury in SDT rat glomeruli and the effect of angiotensin II receptor blocker treatment in the early stage have not been reported in detail. Therefore, we have evaluated early stages of glomerular podocyte damage and the beneficial effect of early treatment with losartan in SDT rats using desmin as a sensitive podocyte injury marker. Moreover, we have developed an automated, computational glomerulus recognition method and illustrated its specific application for quantitatively studying glomerular desmin immunoreactivity. This state-of-the-art method enabled automatic recognition and quantification of glomerular desmin-positive areas, eliminating the need to laboriously trace glomerulus borders by hand. The image analysis method not only enabled assessment of a large number of glomeruli, but also clearly demonstrated that glomerular injury was more severe in the juxtamedullary region than in the superficial cortex region. This applied not only in SDT rat diabetic nephropathy but also in puromycin aminonucleoside-induced nephropathy, which was also studied. The proposed glomerulus image analysis method combined with desmin immunohistochemistry should facilitate evaluations in preclinical drug efficacy studies as well as elucidation of the pathophysiology of diabetic nephropathy.

Mulberry leaf extract intake reduces hyperglycaemia in streptozotocin (STZ)-induced diabetic rats fed high-fat diet

This study evaluated the antioxidant activity and anti-diabetic effect of mulberry (Morus alba L. wielkolistna zolwinska) leaf extracts in diabetic rats fed a high-fat diet. After initial 4-week high-fat diet, streptozotocin was injected in Wistar rats to induce non-obese type 2 diabetes. After confirmation of diabetes, animals were treated with mulberry dried leaves, leaf-derived ethanol or acetone extracts added to high-fat diet for 4 weeks. Mulberry ethanol extract with higher level of phenolics – chlorogenic acid and flavonol glucosides was more effective than acetone extract or dry leaves in the lowering of blood glucose, increasing insulin level and markers of antioxidant activity. The results confirm key mechanisms related to the effect of mulberry and its bioactive components on modulation of glucose metabolism through correcting hyperglycaemia, increasing insulin secretion, and improving antioxidant status in STZ-induced non-obese diabetic rat model. Antidiabetic effects exerted by mulberry leaves might depend on the extraction process.

A Critical Review of the Role of Roux-en-Y Gastric Bypass in Treatment Resistant Non-obese Type II Diabetic Patients

Diabetes Mellitus continues to be a growing global problem with millions of new cases yearly. A majority of patients have co-morbid conditions including, but not limited to obesity. Advances in the surgical treatment of obesity have made it popular and effective for patients looking for permanent weight loss solutions. Notably, bariatric surgery achieves not only weight loss, but also a dramatic decrease in fasting blood glucose (FBG) and glycosylated hemoglobin (HbA1c) levels. This has led some to investigate whether bariatric surgery, specifically the Roux-en-Y Gastric Bypass (RYGB) procedure, may be an effective treatment for type II diabetes in the non-obese as well as the obese population.

Immunological disorders of diabetes mellitus in experimental rat models.

A comprehensive understanding of the pathogenic mechanism is the prerequisite for proper disease management. However, the mechanisms of diabetes mellitus and diabetic complication remain extremely complicated and unresolved. While immune reactions are involved in the pathogenesis of diabetes and diabetic complication, the diabetic condition itself can influence immune responses. Furthermore, both diabetes and immune reactions are regulated by genetic and environmental factors. As a result, animal models have evolved to be powerful research tools to elucidate the complicated mechanisms for the pathogenesis of diabetes. Recently, various animal models of diabetes have been developed in rats, which provide advantages over mouse models in the scale of tissue samples and variation in type 2 diabetes models. In this review, we introduced rat models of diabetes and summarized the immune reactions in diabetic rats to propose the relationship between immune reactions and diabetes. Type 1 diabetes is induced by self-reactive cellular immune reactions. On the other hand, type 2 diabetes in rat models is associated with augmentation of innate immune reactions and increased humoral immunity. For example, helper T (Th) 1/Th17 cells are prevalent in non-obese type 1 diabetes rats (diabetes-prone BioBreeding rats), while non-obese type 2 diabetes rats (Goto-Kakizaki rat) show higher levels of natural IgM and T cell ratios with elevated Th2 cells compared with Wister rats. The investigation of immunological disorders in various diabetic rat models is useful to elucidate complicated mechanisms for the pathophysiology of diabetes. In future studies, immunological experimentations altering Th1/Th17 or Th2 cell levels and natural immune reactions may lend support to understanding the causes of diabetes and predicting the pathological conditions in diabetes.

Expression of the glucose-sensing receptor T1R3 in pancreatic islet: changes in the expression levels in various nutritional and metabolic states.

We reported recently that the taste type 1 receptor 3 (T1R3), a subunit of the sweet taste receptor, functions as a cell-surface glucose-sensing receptor in pancreatic β-cells. In the present study, we investigated the expression of T1R3 in pancreatic islets. mRNA for T1R2 and T1R3 was detected in mouse pancreatic islets. Quantitatively, the mRNA expression level of T1R2 was less than 1% of that of T1R3. Immunohistochemically, T1R3 was abundantly expressed in mouse islets whereas T1R2 was barely detected. Most immunoreactive T1R3 was colocalized with insulin and almost all β-cells were positive for T1R3. In addition, T1R3 was expressed in some portion of α-cells. Immunoreactivity of T1R3 in β-cells was markedly reduced in fed mice compared to those in fasting mice. In contrast, mRNA for T1R3 was not different in islets of fasting and fed mice. Glucose-induced insulin-secretion was higher in islets obtained from fasting mice compared to those from fed mice. The expression of T1R3 was markedly reduced in islets of ob/ob mice compared to those of control mice. Similarly, the expression of T1R3 was reduced in islet of db/db mice. In addition, the expression of T1R3 was markedly reduced in β-cells of fatty diabetic rats and GK rats, models of obese and non-obese type 2 diabetes, respectively. These results indicate that T1R3 is expressed mainly in β-cells and the expression levels are different depending upon the nutritional and metabolic conditions.

Does Resistin Gene Polymorphisms +299 (G&gt;A) Participate in Insulin Resistance in Egyption Non-obese Type 2 Diabetes?

Background: Insulin Resistance (IR) is a condition which precedes the development of type 2 diabetes mellitus (T2DM). Resistin is a hormone secreted by adipocytes. Resistin gene (RETN) polymorphisms has been found to be associated with obesity and insulin resistance. We choose 60 patients have known type 2 diabetes mellitus against 45 healthy subjects to investigate the relationship between RETN +299 gene polymorphisms and insulin resistance, in non-obese patients with T2DM. Results: The present study revealed statistically significant increase in AA and combined GA+AA genotypes (with ODD Ratio 4.04 and 4.75 respectively), and statistically significant decrease in GG genotype in non-obese T2DM as compared to the control subjects. Also we found statistically significant increase in A allele and serum resistin in T2DM group as compared to the control group. In addition there were statistically significant increase in mean value ± SD of fasting blood glucose, insulin, HOMA-IR, HbA1C%, Resistin, total cholesterol, triglyceride, LDL-C and statistically significant decrease in mean value ± SD in serum HDL-C in AA combined AA+GA subgroups as compared to GG subgroup of T2DM group. Conclusions: Our study has shown that resistin +299G/A is an important genetic regulator that resulted hyperresistinemia and subsequently may be predisposing factor the development of T2DM in non-obese Egyptian population.

Therapeutic properties of VO(dmpp)2 as assessed by in vitro and in vivo studies in type 2 diabetic GK rats

The bis(1,2-dimethyl-3-hydroxy-4-pyridinonato)oxidovanadium(IV), VO(dmpp)2, has shown anti-diabetic effects by in vitro studies in Wistar (W) rat adipocytes and in vivo in obese Zucker rats. The aim of this work is to confirm the therapeutic properties of VO(dmpp)2 in non-obese type 2 diabetic Goto-Kakizaki (GK) rats. An in vivo study was carried out, treating W and GK rats during 21days with a daily dose of VO(dmpp)2 (44μmol/kg). It was shown that VO(dmpp)2 doesn't affect the normal increase of body weight of both W and GK rats, after 8days of treatment ameliorates glycemia in GK rats (8.4±0.3 vs 10.1±0.2mM in GK control, P<0.001) but doesn't interfere with glucose levels in W rats and, after 21days of treatment, improves the glucose intolerant profile of GK rats (13.1±0.5 vs 20.6±0.7mM/min in GK control, P<0.001), despite no increase of plasma insulin levels during glucose tolerance test. Additionally, it was demonstrated that VO(dmpp)2 significantly enhances [3-3H]-glucose uptake by W and GK rat adipocytes (non-toxic concentration of 100μM: respectively 193±20 and 254±21%, P<0.001, relative to the basal value) showing an efficacy similar to insulin 1.72nM and better than the same concentration of BMOV (P<0.01). Western blotting revealed that in W and GK rats VO(dmpp)2 significantly promotes IRS2 (P<0.05) and p-AKT expression (P<0.001 and P<0.05, respectively, relative to the respective controls) and in GK animals reduces the increase of PTP1β expression (P<0.001, relative to GK control).

Dietary Supplementation with (−)-Epigallocatechin-3-gallate Reduces Inflammatory Response in Adipose Tissue of Non-obese Type 2 Diabetic Goto-Kakizaki (GK) Rats

(-)-Epigallocatechin gallate (EGCG), a major catechin in green tea, is an antioxidant associated with the reduction of oxidative stress in vitro. However, the mechanisms underlying the effects of EGCG on adipose tissue-related metabolic disturbances in vivo are not understood. This study examined whether dietary supplementation of EGCG reduces the oxidative stress-associated inflammatory response in the mesenteric adipose tissue of non-obese type 2 diabetic Goto-Kakizaki (GK) rats. GK rats were fed a normal diet or diet containing 0.1, 0.2, or 0.5% EGCG (w/w) for 25 weeks. The mRNA levels of IL-1β were significantly reduced in GK rats given 0.1% EGCG (0.059 ± 0.008; means ± SEM in arbitrary unit) compared with those in GK rats given a control diet (0.135 ± 0.011), but not in those given 0.2% EGCG (0.123 ± 0.012) or 0.5% EGCG (0.112 ± 0.019). The mRNA and protein level of other genes for inflammatory responses such as IL-18, TNF-α, MCP-1, CD11s, CD18, and resistin were also significantly reduced in rats given 0.1% EGCG, but not in those given ≥ 0.2% EGCG. This suggests that supplementation with EGCG at relatively low concentrations (0.1%) in GK rats reduces expression of genes and proteins involved in inflammation in adipose tissue.