Mastoparan-induced hormone release from rat pancreatic islets

Area of Science:

• Endocrinology
• Molecular Pharmacology
• Cell Biology

Background:

• Mastoparan is a tetradecapeptide from wasp venom with known effects on cellular signaling.
• Pancreatic islets are crucial for regulating blood glucose through insulin and glucagon secretion.
• Understanding the mechanisms of hormone release is vital for diabetes research.

Purpose of the Study:

• To elucidate the signaling pathway by which mastoparan stimulates insulin and glucagon release from rat pancreatic islets.
• To investigate the role of specific cellular components, such as GTP-binding proteins, calcium, and various enzymes, in mastoparan-induced hormone secretion.

Main Methods:

• Perifusion and incubation experiments using isolated rat pancreatic islets.
• Pharmacological inhibition using pertussis toxin, neomycin, nifedipine, H-7, somatostatin, and parabromophenacylbromide.
• Measurement of cytosolic free Ca2+ concentration using fura-2 and assessment of hormone synthesis.
• In vivo studies involving intravenous administration of mastoparan in rats.

Main Results:

• Mastoparan induced a dose-related, monophasic release of insulin and glucagon, which was temperature-dependent.
• The response was blocked by pertussis toxin and neomycin, indicating involvement of GTP-binding proteins and phosphoinositide turnover.
• Mastoparan increased cytosolic Ca2+ but did not require Ca2+ influx, protein kinase-A/C, or somatostatin.
• Phospholipase-A2 inhibition affected low-concentration responses but not high-concentration responses.

Conclusions:

• Mastoparan stimulates islet hormone release via a temperature-dependent pathway mediated by pertussis toxin-sensitive GTP-binding proteins.
• Activation of phospholipase-C and subsequent intracellular calcium release are likely coupled to exocytosis.
• Calcium influx and protein kinases A and C are not involved in mastoparan's primary hormone-releasing action.