Insulin secretion, calcium

More recent analysis of tissue specific gene deletions showed that the Cav1.2 channel is involved in a wide variety of function including hippocampal learning, insulin secretion, intestine and bladder motility. Further analysis will be required to unravel the functional significance of voltage-dependent calcium channels for specific cellular functions. 

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. 

The importance of insulin as a mediator of the hypercalciuric effect of arginine infusion was also evident from studies conducted in chronically diabetic rats, where diabetes was induced by strepto-zotocin (23). Animals were injected with streptozotocin prior to arginine infusion 100 mg/kg i.p. was given on the seventh day before, followed by 25 mg/kg six days before the arginine infusion and renal clearance studies. In contrast to non-diabetic controls, diabetic animals did not increase their urinary calcium excreted (per ml glomerular filtrate) in response to the arginine infusion, nor did the arginine stimulate insulin secretion. 

The above experiments strongly suggest to us that a linear relationship exists between serum or plasma insulin levels over a wide physiological range, and urinary calcium excretion. The calciuric response to arginine or glucose infusion does not occur if insulin secretion is prevented, as evidenced by the data obtained from animals made acutely insulinopenic by mannoheptulose, or more chronically diabetic by streptozotocin. 

Mechanism of Action An antihyperglycemic that stimulates release of insulin from beta cells of the pancreas by depolarizing beta cells, leading to an opening of calcium channels. Resulting calcium influx induces insulin secretion. Therapeutic Effect Lowers blood glucose concentration. 

Biden, T.J. Comte, M. Cox, J.A. Wollheim, C.B. Calcium-calmodulin stimulates inositol 1,4,5-trisphosphate kinase activity from insulin-secreting RINm5F cells. J. Biol. Chem., 262, 9437-9440 (1987)... 

Krasnoperov VG, Beavis R, Chepumy OG et al (1996) The calcium-independent receptor of a-latrotoxin is not a neurexin. Biochem Biophys Res Commun 227 868-75 Krasnoperov VG, Bittner MA, Beavis R et al (1997) a-Latrotoxin stimulates exocytosis by the interaction with a neuronal G-protein-coupled receptor. Neuron 18 925-37 Krasnoperov VG, Bittner MA, Mo W et al (2002b) Protein tyrosine phosphatase-G is a novel member of the functional family of a-latrotoxin receptors. J Biol Chem 277 35887-95 Kreienkamp HJ, Zitzer H, Gundelfinger ED et al (2000) The calcium-independent receptor for a-latrotoxin from human and rodent brains interacts with members of the ProSAP/SSTRIP/Shank family of multidomain proteins. J Biol Chem 275 32387-90 Lajus S, Lang J (2006) Splice variant 3, but not 2 of receptor protein-tyrosine phosphatase a can mediate stimulation of insulin-secretion by a-latrotoxin. J Cell Biochem 98 1552-9 Lajus S, Vacher P, Huber D et al (2006) a-Latrotoxin induces exocytosis by inhibition of voltage-dependent K+ channels and by stimulation of L-type Ca2+ channels via latrophilin in [5-cells. J Biol Chem 281 5522-31... 

T. R. Chay Effects of extracellular calcium on electrical bursting and intracellular and luminal calcium oscillations in insulin secreting pancreatic jS-cells. Biophys.J. 1997, 73 1673-1688. 

L. S. Satin and D. L. Cook Calcium current inactivation in insulin-secreting cells is mediated by calcium influx and membrane depolarization. Pfliigers Arch. 1989, 414 1-10. 

Potassium channels play an important role in the control of insulin secretion in (3-pancreatic cells. In a resting (3-pancreatic cell, the membrane potential is maintained below the threshold for insulin secretion by an efflux of potassium ions through the open potassium channels. As glucose levels rise within the cell, ATP production increases, and the change in the APT/ADP ratio leads to the closing of potassium channels. This causes the calcium channels to open, and entering calcium ions signal insulin secretion. Factors that modulate the (3-pancreatic potassium channels can fine-tune the insulin secretion. 

Q10 Sulfonylurea drugs enhance insulin secretion. They bind to the receptors on the /1-cells of the islets of Langerhans, causing a partial depolarization of the cell membrane, influx of calcium ions and a reduction in potassium efflux. The ultimate result is increased insulin secretion. These drugs also increase the sensitivity of the /1-cells to stimuli that cause insulin secretion, possibly by increasing the intracellular levels of a cyclic nucleotide second... 

Calcium transport is essential for insulin secretion, which is therefore inhibited by calcium channel blockers (73). 

Its primary action is inhibiting the release of GH from the pituitary gland. Somatostatin al.so suppresses the release of both insulin and glucagon. It causes a decrease in both cAMP levels and adenylate cyclase activity. It also inhibits calcium ion influx into the pituitary cells and suppresses glucose-induced pancreatic insulin secretion by activating and deactivating potassium ion and calcium ion permeability, respcc-tively. The chemistry. SARs, and potential clinical applications have been reviewed.--- ... 

Another important issue concerns the intracellular buffers used. We have obtained good results with a potassium glutamate/HEPES buffer (see below). Whenever it might be important, the concentrations of free calcium ions have to be carefully controlled by the use of chelators. As the active concentration of free calcium for exocytosis in insulin-secreting cells ranges from 0.1 (xM (basal) to 10 xM (maximal stimulatory levels) with an EC50 at 2 xM, EGTA is a suitable chelator (Vallar ef ai, 1987). 

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