Insulin secretion inhibition

Insulin secretion Inhibition ATP citrate lyase Stimulation... 

METABOLIC EFFECTS Epi elevates the concentrations of glucose and lactate in blood see Chapter 6), and can inhibit a effect) or stimulate (fi effect) insulin secretion inhibition is the predominant effect. Glucagon secretion is enhanced via activation of p receptors of the a cells of pancreatic islets. Epi also decreases the uptake of glucose by peripheral tissues, in part because of its effects on the secretion of insuhn, but also possibly due to direct effects on skeletal muscle. Glycosuria rarely occurs. The effect of Epi to stimulate glycogenolysis in most tissues and in most species involves /3 receptors. 

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. 

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

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. 

DPP-4 is a serine protease that inactivates GLP-1. GLP-1 stimulates insulin secretion and suppresses glucagon release. The inhibition of DPP-4 prolongs the half-life of GLP-1 and brings about beneficial effects on glucose levels and glucose tolerance in type 2 diabetics. Backes et al. [64] report on the parallel optimization of enzyme binding affinity and inhibition, selectivity, ADME properties, and PK (Scheme 19). 

However, there are a number of other miscellaneous biological roles played by this complex. The [Co(NH3)6]3+ ion has been shown to inhibit the hammerhead ribozyme by displacing a Mn2+ ion from the active site.576 However, [Co(NH3)6]3+ does not inhibit ribonuclease H (RNase),577 topoisomerase I,578 or hairpin ribozyme,579 which require activation by Mg2+ ions. The conclusions from these studies were that an outer sphere complex formation between the enzyme and Mgaq2+ is occuring rather than specific coordination of the divalent ion to the protein. These results are in contrast to DNase I inhibition by the same hexaammine complex. Inhibition of glucose-induced insulin secretion from pancreatic cells by [Co(NH3)6]3+ has been found.580 Intracellular injection of [Co(NH3)6]3+ into a neurone has been found to cause characteristic changes to the structure of its mitochondria, and this offers a simple technique to label neuronal profiles for examination of their ultrastructures.581... 

This paper summarizes our evidence that the mechanism involves protein stimulation of insulin secretion, followed rapidly by insulin inhibition of renal calcium reabsorption. In humans, urinary calcium was proportional to peak postprandial insulin levels in several experiments, after either protein or sucrose was fed. 

In rats, infusion of the insulin secretagogues arginine and glucose induced a calciuria proportional to serum insulin levels. Suppression of insulin secretion by mannoheptulose or streptozotocin prevented the calciuria. Parathyroidectomy did not affect arginine-induced hypercalciuria in the rat, so insulin is not inhibiting parathyroid hormone secretion or activity. 

Abndnla R, Matchkov W, Jeppesen PB, Nilsson H, AaUejaer C, Hermansen K. (2008) Rebandioside A directly stimnlates insulin secretion from pancreatic beta cells A glucose-dependent action via inhibition of ATP-sensitive K-channels. Diabetes ObesMetab 10 1074-1085. 

Diazoxide given i.v. causes prominent arteriolar dilation it can be employed in hypertensive crises. After its oral administration, insulin secretion is inhibited. Accordingly, diazoxide can be used in the management of insulin-secreting pancreatic tumors. Both effects are probably due to opening of (ATP-gated) K+ channels. 

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