Insulins secretion

Control of secretion of anterior pituitary hormones also includes inhibition by hormones produced by target organs. For example, CRH stimulates the anterior pituitary to secrete ACTH, which in turn stimulates the adrenal cortex to secrete corticosteroids. Corticosteroids then feed back to inhibit the secretion of ACTH. Feedback mechanisms are important for the control of most hormones. For example, insulin (qv) secretion from the pancreas increases in response to increased blood glucose resulting from ingestion of a meal. Insulin increases tissue uptake and metaboHsm of glucose, which lowers blood glucose and in turn reduces insulin secretion. 

The absorption of sulfonylureas from the upper gastrointestinal tract is faidy rapid and complete. The agents are transported in the blood as protein-bound complexes. As they are released from protein-binding sites, the free (unbound) form becomes available for diffusion into tissues and to sites of action. Specific receptors are present on pancreatic islet P-ceU surfaces which bind sulfonylureas with high affinity. Binding of sulfonylureas to these receptors appears to be coupled to an ATP-sensitive channel to stimulate insulin secretion. These agents may also potentiate insulin-stimulated glucose transport in adipose tissue and skeletal muscle. 

Metformin. Metformin [657-24-9] (1,1-dimethylbiguanide), mol wt 129.17, forms crystals from propanol, mp 218—220°C, and is soluble in water and 95% ethanol, but practically insoluble in ether and chloroform. Metformin, an investigational dmg in the United States, does not increase basal or meal-stimulated insulin secretion. It lowers blood glucose levels in hyperglycemic patients with Type II diabetes but has no effect on blood glucose levels in normal subjects. It does not cause hypoglycemia. Successful metformin therapy usually is associated with no or some weight loss. 

P-Adrenoceptors have been subdivided into P - and P2-adrenoceptors. A third subset called nontypical P-adrenoceptors or P -adrenoceptors have been described but are stiU the subject of debate. In terms of the interactions with various subsets of P-adrenoceptors, some antagonists are nonselective in that they antagonize the effects of activation of both P - and P2-adrenoceptors, whereas others are selective for either P - or P2-adrenoceptors. P - and P2-adrenoceptors coexist in almost all organs but generally, one type predominates. The focus herein is on the clinically relevant P -adrenoceptor-mediated effects on heart and on P2-adrenoceptor-mediated effects on smooth muscles of blood vessels and bronchioles, the insulin-secreting tissue of the pancreas, and skeletal muscle glycogenolysis for side effects profile (36). 

T24.Dyhukt, J. M., Ankarcrona, M., Burkitt, M.,. Sjbholm,. 4.,. Strom, K., Orrenius, S., and Nico-tera, P. (1994). Different prooxidant levels stimulate grownh, trigger apoptosis, or produce necrosis of insulin-secreting RINm5F cells./. Biol. Chem. 269, 30553-30560. 

Type 2 diabetes is a heterogeneous and progressive endocrine disorder associated with insulin resistance (impaired insulin action) and defective function of the insulin-secreting (3-cells in the pancreatic islets of Langerhans. These endocrine disorders give rise to widespread metabolic disturbances epitomised by hyperglycaemia. The present classes of antidiabetic agents other than insulin act to either increase insulin secretion, improve insulin action, slow the rate of intestinal... 

Sulphonylureas Chlorpropamide, glibenclamideb, gliclazide, glimepiride, glipizide, gliquidone, tolazamide, tolbutamide Stimulate insulin secretion (typically 6-24 h) Oral... 

Prandial insulin releasers (meglitinides) Repaglinide, nateglinide Stimulate insulin secretion (rapid and short-acting < 6 h) Oral... 

Incretin mimetic Exenatide Mimic GLP-1C enhance prandial insulin secretion SC injectiond... 

Gliptins (DPP-4 inhibitors) Sitagliptin Inhibit DPP-46 enhance prandial insulin secretion Oral... 

Although the main therapeutic effect of sulphonylureas is increased insulin secretion, there is evidence that... 

In clinical studies, selective DPP-4 inhibition increased active circulating concentrations of GLP-1 and GEP by two- to threefold. This was associated with increased glucose-induced insulin secretion and suppression of glucagon secretion, although changes in satiety and gastric emptying have not been repotted. 

The first hormonal signal found to comply with the characteristics of both a satiety and an adiposity signal was insulin [1]. Insulin levels reflect substrate (carbohydrate) intake and stores, as they rise with blood glucose levels and fall with starvation. In addition, they may reflect the size of adipose stores, because a fatter person secretes more insulin than a lean individual in response to a given increase of blood glucose. This increased insulin secretion in obesity can be explained by the reduced insulin sensitivity of liver, muscle, and adipose tissue. Insulin is known to enter the brain, and direct administration of insulin to the brain reduces food intake. The adipostatic role of insulin is supported by the observation that mutant mice lacking the neuronal insulin receptor (NDRKO mice) develop obesity. 

Ashcroft FM (2005) ATP-sensitive potassium channelo-pathies focus on insulin secretion. J Clin Invest 115 2047-2055... 

BAYK8644 is a DHP with Ca2+ channel activating properties. Although some therapeutic effects can be envisaged for such drugs (such as stimulation of glucose-dependent insulin secretion, positive inotropy), severe side effects are also predicted from animal studies (dystonic neurobehavioral syndrome, hypertension, arrhythmias), which currently prevents their clinical development. 

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. 

GLUT2 is a glucose/fructose transport facilitator expressed in liver, small intestine, kidney, and pancreatic p-cells. GLUT2 has low-affinity for glucose (Km= 60 mM) and fructose (ivm=65 mM), and is an essential part of the glucose sensor of pancreatic (3-cells which controls insulin secretion and biosynthesis. 

Incretins gut hormones that increase glucose-stimulated insulin secretion GLP-1 glucagon-like peptide-1 GDP Gastric inhibitory peptide or glucose-dependent insulino-tropic peptide... 

An oral glucose load increases insulin secretion more efficiently than when glucose is administered... 

Incretin Hormones. Figure 2 The incretin effect. Patients underwent an oral or equivalent intravenous glucose load so that the glycemic profiles became similar. In such conditions, the data show that the oral glucose load is more potent to stimulate insulin secretion than an equivalent intravenous glucose stimulus. 

GDP) was isolated. It was characterized as being released by the duodenum following an oral glucose load and increasing glucose-stimulated insulin secretion. However, this pqDtide was not able to account fully for the... 

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