Somatostatin inhibition of Ca2(+)-induced insulin secretion in permeabilized HIT-T15 cells

Area of Science:

• Endocrinology
• Cell Biology
• Molecular Pharmacology

Background:

• Somatostatin is a hormone known to regulate various physiological processes, including hormone secretion.
• Insulin secretion from pancreatic beta-cells is a complex process involving calcium influx and exocytosis.
• The precise mechanism by which somatostatin inhibits insulin secretion, particularly at the cellular level, requires further elucidation.

Purpose of the Study:

• To investigate the role of G-proteins in somatostatin-mediated inhibition of insulin secretion.
• To determine the specific stage of the exocytosis pathway affected by somatostatin.
• To elucidate the signaling requirements for somatostatin's inhibitory action on insulin release.

Main Methods:

• Utilized permeabilized HIT-T15 cells (a pancreatic beta-cell line) to study intracellular signaling.
• Assessed calcium (Ca2+)-induced insulin secretion in response to somatostatin.
• Investigated the requirement for guanosine triphosphate (GTP) and the effect of pertussis toxin on somatostatin's action.

Main Results:

• Somatostatin inhibited Ca2(+)-induced insulin secretion in permeabilized cells, showing reduced sensitivity compared to intact cells.
• The inhibitory effect of somatostatin was dependent on the presence of GTP; GDP could not replace GTP.
• Pre-treatment with pertussis toxin eliminated the inhibitory effect of somatostatin on insulin secretion.

Conclusions:

• Somatostatin inhibits insulin secretion by activating a G-protein.
• This G-protein-mediated inhibition occurs downstream of soluble intracellular messenger generation.
• The mechanism involves interference with the exocytosis process, distal to initial signaling events.