Obesity is a common disorder affecting millions of people worldwide. The number of overweight and obese subjects, globally, is currently 2 billion and 800 million, respectively. Projected estimates show that the number of overweight citizens will approach 60% of the world's population by the year 2030. Oxidative stress facilitates the development of obesity by stimulating pre-adipocyte differentiation and eventual adipose accumulation. Large deposits of fat release excessive quantities of adipocytokines, resulting in chronic inflammation. The obesity-induced chronic inflammation paves the way for a large variety of systemic complications including but not limited to diabetes mellitus, hyperlipidemia, atherosclerotic lesions, cardiovascular diseases tissue and malignancy. In addition, other obesity-inducers, such as increased insulin growth factor 1, insulin resistance, and increased tissue level of leptin and low concentration of adiponectin may lead to the development of tissue malignancy. Increased physical activity coupled with a healthy food intake is crucial to the management of obesity. Anti-obesity drugs such as sibutramine, qsymia (a combination of phentermine and topiramate), and orlistat have been used to treat obesity with variable degrees of efficacy. Bariatric surgery becomes a choice in severe cases when physical activity and pharmacotherapy fail. In the obese patient with diabetes mellitus, the choice of hypoglycemic agent is important. Metformin,

Nociceptin (NC), also known as Orphanin FQ, is a brain peptide involved in the regulation of pain, but its role in the endocrine pancreas is poorly understood. The present study examines the pattern of distribution of NC and its effect on insulin and glucagon secretion after the onset of diabetes mellitus (DM). Male Wistar rats weighing 150-200 g were made diabetic with streptozotocin (60 mg/kg body weight, intraperitoneally). Four weeks after the induction of DM, pancreatic tissues were retrieved and processed for immunofluorescence, immunoelectron microscopy, and insulin and glucagon secretion. Isolated islets from non-diabetic and diabetic rats were used to determine the effect of NC on insulin release. NC was discerned in islet cells of non-diabetic control and diabetic rat pancreata. NC co-localized only with insulin in pancreatic beta cells. NC did not co-localize with either glucagon or somatostatin or pancreatic polypeptide. The number of NC-positive cells was markedly (p < 0.001) reduced after the onset of DM. Electron microscopy study showed that NC is located with insulin in the same secretory granules of the beta cells of both non-diabetic and diabetic rat pancreas. NC inhibits insulin release markedly (p < 0.05) from pancreatic tissue fragments of non-diabetic and diabetic rats. In contrast, NC at 10 M stimulates insulin release in isolated islets of DM rats. In conclusion, NC co-localizes with insulin only in the islet of Langerhans. The co-localization of NC with insulin suggests a role for NC in the regulation of pancreatic beta cell function.

Nociceptin (NC) consists of 17 amino acids (aa) and takes part in the processing of learning and memory. The role of NC in the induction of endogenous antioxidants in still unclear. We examined the effect of NC on the expression of endogenous antioxidants in kidney, liver, cerebral cortex (CC), and hippocampus after the onset of diabetes mellitus, using enzyme-linked immunosorbent assay and immunohistochemistry. Exogenous NC (aa chain 1–17; 10 µg/kg body weight) was given intraperitoneally to normal and diabetic rats for 5 days. Our results showed that catalase (CAT) is present in the proximal (PCT) and distal (DCT) convoluted tubules of kidney, hepatocytes, and neurons of CC and hippocampus. The expression of CAT was significantly (p < 0.05) reduced in the kidney of normal and diabetic rats after treatment with NC. However, NC markedly (p < 0.001) increased the expression CAT in the liver and neurons of CC of diabetic rats. Superoxide dismutase (SOD) is widely distributed in the PCT and DCT of kidney, hepatocytes, and neurons of CC and hippocampus. NC significantly (p < 0.001) increased the expression of SOD in hepatocytes and neurons of CC and the hippocampus but not in the kidney. Glutathione reductase (GRED) was observed in kidney tubules, hepatocytes and neurons of the brain. NC markedly increased (p < 0.001) the expression of GRED in PCT and DCT cells of the kidney and hepatocytes of liver and neurons of CC. In conclusion, NC is a strong inducer of CAT, SOD, and GRED expression in the kidney, liver and brain of diabetic rats.

Spexin is a newly discovered gastrointestinal tract (GIT) peptide. Preliminary biochemical analysis showed that spexin was localized to secretory granules in a transfected pancreatic cell line. Spexin was also expressed in the submucosal cells of the mouse stomach indicating that it is a resident peptide in the GIT and may thus influence pancreatic function. It has been suggested that spexin may play a role in the regulation of physiological homeostasis. Our aim was to determine whether spexin is present in the pancreas of normal and streptozotocin‐induced diabetic rats. We also wanted to know whether spexin co‐localizes with pancreatic hormones in the islet of Langerhans. Immunohistochemical, immunofluorescence and transmission electron microscopy (TEM) methods were used to determine the cellular localization of spexin in the endocrine pancreas of non‐diabetic and diabetic rats. Immunofluorescence study showed that a significant number of cells in the core of rat pancreatic islet contains spexin, where insulin‐positive cells are located. We used double labelling immunofluorescence method to determine whether spexin and insulin co‐localize together in the same cell. We observed that these spexin‐immunoreactive cells also contain insulin. There was no evidence of co‐localization of spexin with either somatostatin or pancreatic polypeptide. The number of spexin‐ and insulin‐immunopositive cells was significantly (p <0.05) reduced after the onset of diabetes mellitus. Moreover, TEM showed that the secretory granules of pancreatic beta cells contain spexin‐labelled immunogold particles. In conclusion, the presence of spexin in pancreatic beta cells suggests a role in the regulation of pancreatic endocrine function.