Diabetes mellitus type insulin secretion

Gerich, J.E. 1998. The genetic basis of type 2 diabetes mellitus impaired insulin secretion versus impaired insulin sensitivity. Endocr. Rev. 19 491-503. 

T Diabetes mellitus, caused by a deficiency in the secretion or action of insulin, is a relatively common disease nearly 6% of the United States population shows some degree of abnormality in glucose metabolism that is indicative of diabetes or a tendency toward the condition. There are two major clinical classes of diabetes mellitus type I diabetes, or insulin-dependent diabetes mellitus (IDDM), and type II diabetes, or non-insulin-dependent diabetes mellitus (NIDDM), also called insulin-resistant diabetes. 

Type 2 Diabetes Mellitus This is the most prevalent form of diabetes and is characterized by both an insulin secretion defect and insulin resistance. Maturity-onset diabetes of the young (MODY), attributable to mutations of the glucose kinase gene (discussed earlier), may also be classified as type 2 diabetes mellitus. Obesity is a contributory factor and may predispose to insulin resistance with eventual development of type 2 diabetes mellitus. The precise mechanism by which obesity leads to insulin resistance in the target tissues is not understood. However, in several animal models (e.g., ob/ob mouse, db/db mouse) mutations have been identified that cause both obesity and diabetes mellitus. Unlike type 1 diabetes mellitus, type 2 is not an autoimmune disease. Studies with monozygotic twins have revealed a 90% concordance rate for type 2 diabetes mellitus, suggesting the involvement of genetic factors in the development of the disease. 

Blood sugar (blood glucose) in human beings is controlled by the secretion of (—>) insulin by the beta (B- or (3-) cells of the islands of Langerhans in the pancreas. Loss of insulin synthesis leads to (—>) diabetes. Type 1 diabetes (insulin dependent diabetes mellitus, EDDM) begins in juveniles as an organ-specific autoimmune reaction, the destructive insulitis. 

Diabetes mellitus is defined as hyperglycaemia (fasting > 7 mM and/or 2 h postprandial >11.1 mM) due to absolute or relative lack of insulin. The most common forms are type 1 diabetes (prevalence 0.25%), with absolute lack of insulin, and type 2 diabetes (prevalence 4-6%) which is due to the combination of insulin resistance and insufficient insulin secretion. 

CF-related diabetes shares characteristics of both type 1 and type 2 diabetes mellitus but is categorized separately. The primary cause of CFRD is insulin deficiency resulting from both reduced functional pancreatic islet cells and increased islet amyloid deposition. Insulin secretion is delayed in response to glucose challenge, and absolute insulin secretion over time is reduced. Some insulin resistance may also be present in CFRD however, sensitivity may be increased in CF patients without diabetes.8... 

Sitagliptin is a dipeptidylpeptidase-4 inhibitor that increases insulin secretion and lowers glucagon secretion. Sitagliptin is available for oral administration. It is indicated in patients with type 2 diabetes mellitus in combination with either metformin (biguanide) or a sulphonylurea or a thiazolidinedione. 

Diabetes mellitus is characterized by hypergly-caemia and disturbances of carbohydrate, fat and protein metabolism that are associated with absolute or relative deticiencies in insulin action and/or insulin secretion. Although diabetes is an endocrine deficiency or resistance state its major manifestations are those of metabolic disease with wide ranging tissue effects. Insulin resistance does exist in type 2 diabetes, however it is also exists in many individuals without diabetes. It is difficult to accept insulin resistance is the sole determining pathogenic factor in type 2 diabetes. Therefore, it is more appropriate to describe type 2 diabetes as a condition of /3-cell dysfunction in an insulin resistance background. 

Insulin Preparations. Since diabetes mellitus is a defect of one or more of insulin production, secretion, or action, the administration of insulin replacement as a treatment for diabetes in the 1920s was a landmark discovery. Historically, most commercial insulin came from either bovine or porcine sources. Beef insulin differs from human insulin by three amino acid substitutions pork insulin differs by only one residue. For many years, standard insulin preparations were 70% beef and 30% porcine. However, the biosynthesis of human insulin has now displaced the animal insulins, especially bovine insulin which was more antigenic. Mass production of human insulin by recombinant DNA methods is achieved by inserting the human proinsulin gene into either E. coli or yeast and treating the resulting proinsulin to yield the human insulin molecule. Insulin preparations may be divided into four major types ... 

Over 5% of the population of western nations is afflicted with diabetes. TTie most prevalent form of diabetes, non-insulin-dependent diabetes mellitus (NIDDM, or type 11), is commonly associated with obesity and hypertension, and is believed to be the consequence of altered insulin action or insulin secretion (for review see Defronzo, 1988 Defronzo and Ferrannini, 1991). Insulin-dependent diabetes mellitus (IDDM, or type 1 diabetes) accounts for approximately 10% of all cases of diabetes. IDDM is characterized by specific destruction of insulin secreting /3-cells found in islets of Langerhans. Destruction of 80-90% of islet /3-cells causes insulin deficiency and the inability to regulate blood glucose levels. 

Diabetes mellitus is defined as an elevated blood glucose associated with absent or inadequate pancreatic insulin secretion, with or without concurrent impairment of insulin action. The disease states underlying the diagnosis of diabetes mellitus are now classified into four categories type 1, insulin-dependent diabetes) type 2, non-insulin-dependentdiabetes) type 3, other, and type 4, gestational diabetes mellitus (Expert Committee, 2003). 

The current classification of diabetes mellitus identifies a group of patients who have virtually no insulin secretion and whose survival depends on administration of exogenous insulin. This insulin-dependent group (type 1) represents 5-10% of the diabetic population in the USA. Most type 2 diabetics do not require exogenous insulin for survival, but many need exogenous supplementation of their endogenous secretion to achieve optimum health. 

Several tests use glucagon to diagnose endocrine disorders. In patients with type 1 diabetes mellitus, a classic research test of pancreatic beta-cell secretory reserve uses 1 mg of glucagon administered as an intravenous bolus. Because insulin-treated patients develop circulating anti-insulin antibodies that interfere with radioimmunoassays of insulin, measurements of C-peptide are used to indicate beta-cell secretion. 

Low LPL activity can also be found secondary to metabolic dysregulation, notably in insulin resistance and type 2 diabetes mellitus. In fact, diabetic hypertriglyceridemia is caused in part by decreased LPL secretion in response to reduced insulin action. Another preanalytical pitfall results from the high affinity of LPL for triglyceride-rich lipoproteins. When extremely hypertriglyceridemic plasma is prepared by cen-... 

Kahn SE, Montgomery B, Howell W, Ligueros-Saylan M, Hsu CH, Devineni D, McLeod JF, Horowitz A, Foley JE. Importance of early phase insulin secretion to intravenous glucose tolerance in subjects with type 2 diabetes mellitus. J Clin Endocrinol Metab 2001 86(12) 5824-9. 

The islet cells of the pancreas synthesize and secrete insulin and glucagon. These hormones are important in regulating glucose uptake and use, as well as in other aspects of energy metabolism. Problems in the production and effects of insulin are typical of a disease known as diabetes mellitus. Diabetes mellitus can be categorized into two primary forms type 1 diabetes, which is caused by an absolute deficiency of insulin, and type 2 diabetes, which is caused by a decrease in peripheral insulin effects, combined with abnormal insulin release. 

---