**Abstract**

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.

**Keywords:** Gut microbiota, diabetes mellitus, probiotics, pancreas

### **1. Introduction**

Insulin is predominantly the most important endogenous protein responsible for the physiological regulation of metabolism [1]. Exogenous insulin is the only substantial treatment option for patients suffering from insulin deficiency since the initial discovery of insulin by Sir Frederick G Banting and its purification by James B. Collip in 1921 [2, 3]. The pancreatic gland is responsible for the regulated secretion of insulin to maintain glucose homeostasis under different physiological conditions [4, 5]. Islets of Langerhans present in the pancreas contain cells that secret specific hormones which help in maintaining glucose levels during feeding and fasting [5–9]. Islets of Langerhans are defined as closed areas containing multiple cell types with enormous vascular and nervous innervation [5]. Islets of Langerhans are designated as the endocrine portion of the pancreas. The exocrine part of the pancreas surrounds islets of Langerhans. Different cell types present in the islets secrete different types of hormones. Islets contain four different types of endocrine cells: alpha (α) cells (glucagon), beta (β) cells (insulin), delta (δ) cells (somatostatin) and PP cells (pancreatic polypeptide) [5]. Alpha cells are responsible for the secretion of glucagon hormone to enhance blood glucose levels under fasting conditions while β cells are responsible for insulin secretion which initiates postprandial glucose metabolism and thus controls the rising blood glucose levels [10, 11]. Apart from glucose metabolism, insulin is also involved in lipid and protein metabolism [12–14]. Blood glucose level acts as the main trigger for the release of insulin from β cells, a phenomenon known as glucose-stimulated insulin secretion (GSIS) [15–17]. Glucose at normal physiological levels not only induces insulin gene transcription by recruiting transcription factors (PDX-1, MafA and NeuroD) but also improves the insulin mRNA stability thus acting as a major physiologic regulator of insulin [18–20]. Glucose enters the β cells via glucose-specific channels present on the cell membrane commonly known as glucose transporters (GLUT) [4, 17]. Numerous types of glucose transporters are present in different tissue of the body [21]. But specifically, GLUT2 is most abundant and functional in the pancreas (β cells) and liver (hepatocytes) whereas GLUT4 is present on skeletal and cardiac muscles and adipocytes [21, 22].
