High Energy Intake Induced Overexpression of Transcription Factors and Its Regulatory Genes Involved in Acceleration of Hepatic Lipogenesis: A Rat Model for Type 2 Diabetes.

Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by impaired insulin action and its secretion. The objectives of the present study were to establish an economical and efficient animal model, mimicking pathophysiology of human T2DM to understand probable molecular mechanisms in context with lipid metabolism. In the present study, male Wistar rats were randomly divided into three groups. Animals were fed with high fat diet (HFD) except healthy control (HC) for 12 weeks. After eight weeks, intra peritoneal glucose tolerance test was performed. After confirmation of glucose intolerance, diabetic control (DC) group was injected with streptozotocin (STZ) (35 mg/kg b.w., i.p.). HFD fed rats showed increase (p ≤ 0.001) in glucose tolerance and HOMA-IR as compared to HC. Diabetes rats showed abnormal (p ≤ 0.001) lipid profile as compared to HC. The hepatocyte expression of transcription factors SREBP-1c and NFκß, and their target genes were found to be upregulated, while PPAR-γ, CPT1A and FABP expressions were downregulated as compared to the HC. A number of animal models have been raised for studying T2DM, but the study has been restricted to only the biochemical level. The model is validated at biochemical, molecular and histopathological levels, which can be used for screening new therapeutics for the effective management of T2DM.

Adipocytokines and anthropometric measures in type 2 diabetics.

AIM: Type 2 diabetes mellitus has assumed pandemic proportions worldwide. Aggressive management of hyperglycemia in diabetics is a primary goal of treatment. We have previously reported favorable effects of oral hypoglycemic agents on adipocytokines. Aim of the present study was to investigate the relationship of adipocytokines with anthropometric measures and biochemical parameters in type 2 diabetics. METHODS: Clinically diagnosed type 2 diabetics and age, gender matched healthy volunteers were recruited for study. Anthropometric measurements like height, weight, waist-circumference, hip-circumference were recorded and BMI, waist-hip ratio were calculated. Fasting blood samples were collected from participants and sera were analyzed for glucose, glycated haemoglobin, total cholesterol, SGOT, SGPT, insulin, adiponectin and leptin. Correlation of adipocytokines with anthropometric and biochemical parameters was assessed in healthy and diabetic individuals. RESULTS: BMI and WHR in diabetics were significantly higher than healthy population. BMI did not show significant association with adipocytokines. Diabetic males with WHR≥0.9 showed negative association with adiponectin and positive association with leptin. WC did not show significant association with adipocytokines in males. Irrespective of WC, healthy females exhibited positive association with leptin. Diabetic females with WC≥88cm showed leptin to be positively associated with WC. Such association of adipocytokines with WHR was not detected in females. CONCLUSIONS: Body fat distribution can be considered as a parameter in assessing adipokine imbalance. Central adiposity is a better measure of adipokine imbalance than BMI. Abdominal obesity in diabetics correlates with altered levels of adipocytokines indicating its importance in diabetic individuals.

Circulatory adipocytokines and lipid profile variations in type-2 diabetic subjects: desirable side-effects of antidiabetic drugs.

AIM: Inspite of availability of a variety of drugs to treat type 2 diabetes, little is known about their effects on other systems. Normalization of glucose metabolism by these drugs may consequently affect the secretory function in adipocytes. Secretory adipocytokines like adiponectin and leptin are emerging as novel therapeutic targets for type 2 diabetes mellitus (T2DM). The present study was undertaken to analyze the effects of commonly used Oral Hypoglycemic Agents (OHAs) alone, or in combination with other drugs and/or insulin on circulatory adiponectin and leptin levels, lipid profile, and blood pressure in diabetic subjects. METHODS: The study was undertaken at IRSHA and Bharati Vidyapeeth Medical College and Hospital, MS, India. Clinically diagnosed T2DM subjects and age, gender matched healthy controls were recruited. Fasting blood was collected from each subject and the blood samples were analyzed for circulatory adipocytokines and lipid parameters using commercial kits. RESULTS: Serum adiponectin levels were significantly increased while leptin significantly decreased in diabetic men (p<0.05) and women (p<0.001) on OHA, as compared to healthy controls. Triglyceride levels significantly decreased (p<0.05) in diabetic men, however, they remained unchanged in women despite same drug treatment. Serum HDL and LDL levels (p<0.001) were significantly lower in diabetic women as compared to healthy women. Systolic (p<0.05) and diastolic (p<0.001) blood pressure was significantly high in diabetic men but remained unchanged in women. CONCLUSIONS: Frequently used OHAs significantly improve circulatory levels of adipocytokines. Selecting best treatment option for each patient is a key, and 2012 European Association for the Study of Diabetes (EASD) and ADA guidelines recommend diabetes treatment to be individualized depending on various socioeconomic and lifestyle factors. We recommend regular analysis of circulatory adipocytokines in T2DM patients to help clinicians select the best treatment option to normalize levels of these important therapeutic targets.