Beneficial metabolic effects caused by persistent activation of beta-cell M3 muscarinic acetylcholine receptors in transgenic mice.

Previous studies have shown that β-cell M(3) muscarinic acetylcholine receptors (M3Rs) play a key role in maintaining blood glucose homeostasis by enhancing glucose-dependent insulin release. In this study, we tested the hypothesis that long-term, persistent activation of β-cell M3Rs can improve glucose tolerance and ameliorate the metabolic deficits associated with the consumption of a high-fat diet. To achieve the selective and persistent activation of β-cell M3Rs in vivo, we generated transgenic mice that expressed the Q490L mutant M3R in their pancreatic β-cells (β-M3-Q490L Tg mice).

Physiologic implications of phosphoinositides and phospholipase C in the regulation of insulin secretion.

The secretion of insulin from the pancreatic beta-cell must be commensurate to satisfy the insulin requirements of the organism. This cell has a great flexibility to meet these requirements which are increased not only by the ingestion of nutrients (increase of plasma glucose) but also by the sensitivity of target tissues to insulin as well. The insulin secretion is a complex biochemical event regulated by a host of potential second messenger molecules acting alone or in concert.

Switching of G-protein usage by the calcium-sensing receptor reverses its effect on parathyroid hormone-related protein secretion in normal versus malignant breast cells.

The calcium-sensing receptor (CaR) is a G-protein-coupled receptor that signals in response to extracellular calcium and regulates parathyroid hormone secretion. The CaR is also expressed on normal mammary epithelial cells (MMECs), where it has been shown to inhibit secretion of parathyroid hormone-related protein (PTHrP) and participate in the regulation of calcium and bone metabolism during lactation. In contrast to normal breast cells, the CaR has been reported to stimulate PTHrP production by breast cancer cells.

Enhanced activation of phospholipase C and insulin secretion from islets incubated in fatty acid-free bovine serum albumin.

Incubation in 100 micromol/L fatty acid-free bovine serum albumin (FAF-BSA) significantly amplifies insulin secretion from isolated, perifused rat islets. When compared with the responses of control islets incubated in 100 micromol/L radioimmunoassay-grade BSA, insulin secretion rates were increased 2- to 3-fold when these islets were stimulated with 10 mmol/L glucose alone or with the combination of 10 mmol/L glucose, 15 mmol/L KCl, and 100 micromol/L diazoxide. These amplified secretory responses were paralleled by significant increases in the phospholipase C (PLC) activation monitored by fractional increases in (3)H-inositol efflux from these same islets.

Biphasic insulin secretion from freshly isolated or cultured, perifused rodent islets: comparative studies with rats and mice.

In the present report, we compared the insulin secretory responses of freshly isolated, perifused rat and mouse islets to glucose. Prestimulatory glucose levels were changed to assess their influence on the subsequent secretory responses. Additional studies included experiments with the incretin factor glucagon-like peptide-1 (GLP-1), the cholinergic agonist carbachol, and the alpha2 agonist epinephrine.