Ca2+ signaling in mouse pancreatic polypeptide cells

Area of Science:

• Endocrinology
• Cellular Physiology
• Molecular Biology

Background:

• Pancreatic polypeptide (PP)-secreting cells are found in mouse islets of Langerhans.
• Understanding calcium (Ca2+) signaling in these cells is crucial for comprehending islet function.

Purpose of the Study:

• To investigate the Ca2+ signaling mechanisms in mouse pancreatic polypeptide (PP)-secreting cells.
• To identify the specific pathways and channels involved in regulating intracellular Ca2+ concentration ([Ca2+]i).

Main Methods:

• Isolation of PP-secreting cells from mouse islets of Langerhans.
• Measurement of cytoplasmic Ca2+ concentration ([Ca2+]i) using fluorescence indicators.
• Immunocytochemistry for cell identification.
• Pharmacological manipulation using agonists (carbachol, epinephrine, tolbutamide, glucose), antagonists (atropine, methoxyverapamil), and modulators (diazoxide, adenylate cyclase activator, protein kinase A inhibitor, somatostatin).

Main Results:

• Most PP-cells exhibited a rise in [Ca2+]i in response to carbachol (muscarinic) and epinephrine (beta-adrenergic, cAMP-mediated).
• These responses involved depolarization and opening of voltage-dependent Ca2+ channels, as evidenced by inhibition with methoxyverapamil and diazoxide.
• PP-cells possess ATP-dependent K+ (K(ATP)) channels, responding to tolbutamide and high glucose with elevated [Ca2+]i.
• Somatostatin inhibited carbachol-, epinephrine-, tolbutamide-, and glucose-induced [Ca2+]i increases.

Conclusions:

• Glucose directly stimulates PP-cells, with potential masking by local somatostatin.
• PP-cells utilize fundamental regulatory mechanisms, including K(ATP) and voltage-dependent Ca2+ channels, similar to other islet cells.
• These findings contribute to understanding the complex regulation of pancreatic polypeptide secretion and islet cell function.