Gymnema sylvestre is traditionally used as an herbal remedy for diabetes. The effect of Gymnema sylvestre supplementation on beta cell and hepatic activity was explored in an alloxan-induced hyperglycemic adult rat. Animals were made hyperglycemic via a single inj. (i.p) of Alloxan. Gymnema sylvestre was supplemented in diet @250 mg/kg and 500 mg/kg b.w. Animals were sacrificed, and blood and tissues (pancreas and liver) were collected for biochemical, expression, and histological analysis. Gymnema sylvestre significantly reduced blood glucose levels with a subsequent increase in plasma insulin levels in a dosage-dependent manner. Total oxidant status (TOS), malondialdehyde, LDL, VLDL, ALT, AST, triglyceride, total cholesterol, and total protein levels were reduced significantly. Significantly raised paraoxonase, arylesterase, albumin, and HDL levels were also observed in Gymnema sylvestre treated hyperglycemic rats. Increased mRNA expression of Ins-1, Ins-2, Gck, Pdx1, Mafa, and Pax6 was observed, while decreased expression of Cat, Sod1, Nrf2, and NF-kB was observed in the pancreas. However, increased mRNA expression of Gck, Irs1, SREBP1c, and Foxk1 and decreased expression of Irs2, ChREBP, Foxo1, and FoxA2 were observed in the liver. The current study indicates the potent effect of Gymnema sylvestre on the transcription modulation of the insulin gene in the alloxan-induced hyperglycemic rat model. Enhanced plasma insulin levels further help to improve hyperglycemia-induced dyslipidemia through transcriptional modulation of hepatocytes.

Recent reports of diabetes susceptibility loci located on the non-coding regions of the genome highlight the importance of epigenetic control in health and disease. Specifically, microRNAs have shown to have an important regulatory role in pancreatic ß cell physiology. Human studies implicated that ß cell mass and function are regulated by microRNAs in health and disease. Further, the microRNAs are also implicated in ensuing diabetic complications. Delineating the peculiar role of microRNAs in ß cell physiology and pathophysiology will fill the missing gaps in our current knowledge and help to devise better treatment regimens for diabetes. This chapter will discuss multiple effects of different microRNAs on the ß cell physiology in the context of maintenance and function in Type 2 diabetes mellitus.

Appropriate metabolic regulation is vital for health. Multiple factors play important roles in maintaining the metabolic system in different physiological conditions. These factors range from intestinal metabolism of food and absorption of nutrients, pancreatic hormones and their interplay under feeding and fasting, hepatic regulation of macronutrient formation and metabolism storage of macronutrients in skeletal muscles. Intestinal metabolism of ingested food and subsequent nutrient absorption depends on the symbiotic microbial community residing in the gut. The specific ratio of different microbial phyla in the gut has proved to be extremely important for the beneficial role of the gut microbiome. The importance of gut microbiome in the regulation of metabolism has been highlighted with reports of the abnormal ratio of gut microbial community resulting in different metabolic disturbances ranging from obesity to the development of diabetes mellitus. The physiological impact of insulin on the metabolic regulation of macronutrients has recently been shown to be augmented by the secondary metabolites produced by anaerobic fermentation. The current chapter aims to highlight recent findings in the regulation of extraintestinal metabolism by gut microbiome with a specific emphasis on the physiology and pathophysiology of the pancreas in health and disease.