The role of incretins in glucose homeostasis and diabetes treatment.

نویسندگان

  • Wook Kim
  • Josephine M Egan
چکیده

Incretins are gut hormones that are secreted from enteroendocrine cells into the blood within minutes after eating. One of their many physiological roles is to regulate the amount of insulin that is secreted after eating. In this manner, as well as others to be described in this review, their final common raison d'être is to aid in disposal of the products of digestion. There are two incretins, known as glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 (GLP-1), that share many common actions in the pancreas but have distinct actions outside of the pancreas. Both incretins are rapidly deactivated by an enzyme called dipeptidyl peptidase 4 (DPP4). A lack of secretion of incretins or an increase in their clearance are not pathogenic factors in diabetes. However, in type 2 diabetes (T2DM), GIP no longer modulates glucose-dependent insulin secretion, even at supraphysiological (pharmacological) plasma levels, and therefore GIP incompetence is detrimental to beta-cell function, especially after eating. GLP-1, on the other hand, is still insulinotropic in T2DM, and this has led to the development of compounds that activate the GLP-1 receptor with a view to improving insulin secretion. Since 2005, two new classes of drugs based on incretin action have been approved for lowering blood glucose levels in T2DM: an incretin mimetic (exenatide, which is a potent long-acting agonist of the GLP-1 receptor) and an incretin enhancer (sitagliptin, which is a DPP4 inhibitor). Exenatide is injected subcutaneously twice daily and its use leads to lower blood glucose and higher insulin levels, especially in the fed state. There is glucose-dependency to its insulin secretory capacity, making it unlikely to cause low blood sugars (hypoglycemia). DPP4 inhibitors are orally active and they increase endogenous blood levels of active incretins, thus leading to prolonged incretin action. The elevated levels of GLP-1 are thought to be the mechanism underlying their blood glucose-lowering effects.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Incretins in the ICU: is insulin on its way out?

Incretins such as glucagon-like peptide-1 (GLP-1) are gut-derived hormones that stimulate insulin secretion and suppress glucagon secretion, thus playing a key role in glucose homeostasis. While incretin mimetics and enhancers are approved for treatment of outpatients with diabetes, evidence is only starting to accumulate regarding the therapeutic potential of incretins in hospitalized patients...

متن کامل

The Effect of Interval Training on GCK Expression in Hepatocytes and Glucose Homeostasis in Type 2 Diabetes Rats

Objective: Hepatic glucose release plays a potential role in hyperglycemia in type 2 diabetes (T2D) patients. The aim of this experimental study was to determine the effect of 6 weeks of high-intensity interval training (HIIT) on fasting levels of glucose and insulin as well as glucokinase (GCK) expression in liver tissue in obese T2D rats. Materials and Methods: T2D was induced by a high-fat ...

متن کامل

Relationship between gut hormones and glucose homeostasis after bariatric surgery

Type 2 diabetes mellitus (T2D) is emerging as a worldwide public health problem, and is mainly associated with an increased incidence of obesity. Bariatric surgery is currently considered the most effective treatment for severely obese patients. After bariatric surgery, T2D patients have shown a significant improvement in glycemic control, even before substantial weight loss and often discontin...

متن کامل

β‐Cell glutamate signaling: Its role in incretin‐induced insulin secretion

Insulin secretion from the pancreatic β-cell (referred to as β-cell hereafter) plays a central role in glucose homeostasis. Impaired insulin secretion is a major factor contributing to the development of diabetes and, therefore, is an important target for treatment of the disease. Cyclic adenosine monophosphate is a key second messenger in β-cells that amplifies insulin secretion. Incretins rel...

متن کامل

The Effect of Aerobic Exercise on Leptin, Fasting Blood Sugar, Blood Insulin Levels and Insulin Resistant Factor in Patients with Type II Diabetes Mellitus

Background: Diabetes Mellitus is a heterogeneous group of different metabolic disorders that are characterized by chronic increase of blood glucose, cardiovascular diseases, and proteins, lipids and carbohydrate metabolism disorder. Leptin, that is a marker of fat mass in the body, has an important role in the body total metabolism and glucose homeostasis. Aim: To investigate the effect of 12 w...

متن کامل

Designing a glycemic control strategy to maintain glucose homeostasis and prevent hypoglycemia for subjects with type 1 diabetes

This paper presents using the fractional PImDn controller module which manipulates insulin infusion rate to maintain normoglycemia in subjects with type 1 diabetes. To prevent severe hypoglycemia, a conventional proportional controller is used to regulate glucagon infusion rate when the blood glucose levels fall below a threshold. Two sets of controller parameters are obtained and evaluated. Fo...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • Pharmacological reviews

دوره 60 4  شماره 

صفحات  -

تاریخ انتشار 2008