Diabetes mellitus insulin release

Interleukin-1, pancreatic P cells, and insulin-dependent diabetes mellitus Insulin-dependent diabetes mellitus is an autoimmune disease that causes the gradual destruction of insulin-producing pancreatic P cells. It has been postulated that the infiltration of macrophages into the pancreatic islets plays a key role in the destruction of P cells and that cytokines, especially interleukin-1, which is released locally from macrophages, may be the toxic molecule causing this destruction. 

In patients with type 1 insulin-dependent diabetes mellitus not adequately treated with insulin, fatty add release from adipose tissue and ketone synthesis in the liver exceed the ability of other tissues to metabolize them, and a profound, life-threatening ketoaddosis may ocxnir. An infection or trauma (causing an increase in cortisol or epinephrine) may predpitate an episode of ketoaddosis. Patients with type 2 non-insulin-dependent diabetes meUitus (NIDDM) are much less likely to show ketoaddosis. The basis for this observation is not completely understood, although type 2 disease has a much slower, insidious onset, and insulin resistance in the periphery is usually not complete. Type 2 diabetics can develop ketoacidosis after an infection or trauma. In certain populations with NIDDM, ketoaddosis is much more common than previously appredated. 

Diabetes mellitus and hypoglycemia -blockade may prevent the appearance of premonitory signs and symptoms of acute hypoglycemia. -blockade also reduces insulin release it may be necessary to adjust antidiabetic drug dose. 

Oral antidiabetic agents might be indicated in noninsulin dependent diabetes mellitus (NIDDM), i.e. diabetes Type II where insulin resistance caused by down-regulation of insulin receptors or a failure of the pancreas to release insulin even though it is formed, play a role. However, oral antidiabetic... 

Repaglinide en nateglinide are not sulfonylurea agents but their mechanism of action is very alike. Repaglinide is the first carbamoylmethyl-benzoic acid derivative that has been registred for the treatment of diabetes mellitus. It closes ATP-dependent potassium channels in the beta cell membrane with consequent depolarization, opening of calcium channels and increased insulin release. It is rapidly absorbed with peak plasma levels after 1 hour. It has a protein binding of over 98%. 

In type I (juvenile onset) diabetes mellitus, the inability to release insulin (and thus to mobilize glucose... 

Since its isolation in 1921, insulin has been the object of an enormous amount of experimentation aimed at clarifying its mode of action. It is produced by the P cells of the pancreatic islets of Langerhans and released into the bloodstream in response to elevated glucose levels. Tire absence of insulin or of a normal response to insulin results in the condition of diabetes mellitus, which is the most prevalent human metabolic disorder (see Box 17-G).343... 

Several peptide products used in the treatment of diabetes mellitus, in addition to insulin, are currently administered by subcutaneous injection and these drugs are candidates for development of nasal formulations. Glucagon-like peptide-1 (GLP-l)-related peptides stimulate the insulin response to glucose and diminish the release of glucagon after a meal. These effects diminish the excessive postprandial increase in glucose observed after a meal in persons with type 2 diabetes mellitus. GLP-1-related peptides must be administered by subcutaneous injection before meals in order to be effective. This requirement for injection before each meal is likely to impact the utilization of these products by persons with type 2 diabetes. Exendin-4 is a GLP-1-related peptide with a molecular mass of 4.2 kDa. The development of a GLP-1-related peptide nasal formulation containing an absorption enhancer would allow patients to scll-administer one of these drugs just before a meal without the need for a subcutaneous injection. 

Subcutaneous. Injecting medications directly beneath the skin is used when a local response is desired, such as in certain situations requiring local anesthesia. Also, a slower, more prolonged release of the medication into the systemic circulation can be achieved in situations where this is the desired effect. A primary example is insulin injection in a patient with diabetes mellitus. Subcutaneous administration provides a relatively easy route of parenteral injection that can be performed by patients themselves, providing they are properly trained. 

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. 

Thl proinflammatory cytokines such as IFN-y, IL-1/3, IL-12, and TNF-a released by macrophage and T lymphocytes in the vicinity of pancreatic beta cells have been implicated in the pathogenesis of type I (insulin-dependent) diabetes mellitus. Moreover, IL-18 serum levels are increased selectively during the early, subclinical stage of type I diabetes mellitus (N5). 

The majority of individuals afflicted with diabetes mellitus suffer from type 2 diabetes. The onset of type 2 diabetes occurs much later than for type 1 and typically in people over the age of fifty. The pancreas of type 2 diabetics continues to produce and release insulin. However, cells do not respond appropriately to insulin levels in the blood. This condition is known as insulin-resistance and is associated with obesity and high blood pressure. Children who are obese can also develop type 2 diabetes. 

Diabetes mellitus is the result of too little insulin being released from the pancreatic P-cells or of a decrease in the number of active insulin receptors in the target tissue. 

Q7 Ketoacidosis is a serious complication of diabetes mellitus. Because of insulin deficiency and consequent increased availability of fatty acids to the liver, the liver overproduces alpha-hydroxybutyrate and acetoacetic acid, increasing ketone production. The ketones are released into the circulation. They are strongly acidic and, when not effectively buffered, cause metabolic acidosis. Coma may then occur because of severe depression of the nervous system. 

---