Glucose-dependent insulinotropic polypeptide: from pathophysiology to therapeutic opportunities in obesity-associated disorders.

Glucose-dependent insulinotropic polypeptide (GIP) is a hormone secreted from the intestinal K-cells with established insulin-releasing actions. However, the GIP receptor is widely distributed in peripheral organs, including the adipose tissue, gut, bone and brain, where GIP modulates energy intake, cell metabolism and proliferation, and lipid and glucose metabolism, eventually promoting lipid and glucose storage. In diabetes and obesity, the incretin effect of GIP is blunted, while the extrapancreatic tissues keep a normal sensitivity to this hormone. As GIP levels are normal or elevated in obesity and diabetes, mounting evidence from chemical or genetic GIP deletion in animal models of obesity-related diabetes suggests that GIP may have a pro-obesogenic action and that a strategy antagonizing GIP action may be beneficial in these conditions, clearing triglyceride deposits from adipose tissue, liver and muscle, and restoring normal insulin sensitivity. Emerging evidence also suggests that the metabolic benefits of bypass surgery are mediated, at least in part, by surgical removal of GIP-secreting K-cells in the upper small intestine.

Characteristics of liver diseases in the elderly: a review.

Chronic liver diseases are becoming more commonly diagnosed in the elderly, although they are not age-related. Most liver functions in advanced age appear to be well preserved, but some changes in liver morphology and physiology with aging may lead to several differences in clinical course and management of liver diseases in older patients compared to younger. A cautious individual evaluation is therefore required in aged patients, especially concerning reduced hepatic drug clearance and comorbidity. Many chronic liver diseases are characterized by a slow and indolent course with non-specific clinical presentation and this may lead a later diagnosis in the elderly. The presence of an advanced liver disease or cirrhosis is more frequent in old patients as the first clinical presentation. No significant differences in diagnostic investigations or treatment options occur between the elderly and the young. Hepatocellular carcinoma is an affliction of the old patients (mean age 65 age) and follow up with ultrasonography and alpha-fetoprotein is mandatory. Advanced age is not considered a contraindication to liver transplantation, but recipients older than 60 years with poor hepatic synthetic function and comorbidity show a worse prognosis with lower survival rates. This review focuses on new emerging conditions, clinical features and updated therapeutic approaches of the most common chronic liver diseases among the elderly.