Insulin release from human pancreatic islets in vitro

Area of Science:

• Endocrinology
• Metabolism
• Cell Biology

Background:

• Islets of Langerhans are crucial for glucose homeostasis.
• Understanding human islet function is vital for diabetes research.
• Previous studies established effects of various agents on animal islets.

Purpose of the Study:

• To investigate the in vitro insulin secretion response of human islets of Langerhans to various stimuli.
• To assess the stability of glucose-stimulated insulin secretion during tissue culture.
• To compare the effects of different metabolic substrates and modulators on human islet function.

Main Methods:

• Isolation of human islets of Langerhans from a deceased donor pancreas using collagenase digestion.
• Three consecutive periods of in vitro tissue culture for the isolated islets.
• Incubation of islets with various agents, including glucose, mannose, fructose, caffeine, and other metabolic substrates, to measure insulin release.
• Inhibition studies using trifluoperazine to assess its effect on glucose-stimulated insulin release.

Main Results:

• Human islets demonstrated a robust, approximately 5-fold increase in insulin secretion when glucose concentration increased from 2 to 20 mmol/l.
• This glucose-stimulated insulin secretion remained stable throughout the study period across multiple culture and incubation cycles.
• Insulin release was stimulated by mannose, leucine, alpha-ketoisocaproate, dihydroxyacetone, and 3-hydroxybutyrate, but not by fructose or N-acetyl-glucosamine.
• Fructose enhanced insulin release only in the presence of basal glucose (4 mmol/l).
• Caffeine stimulated insulin release independently of glucose and potentiated glucose-induced insulin secretion.
• Trifluoperazine (25 mumol/l) inhibited glucose-stimulated insulin release.

Conclusions:

• Human islets of Langerhans exhibit stable and responsive insulin secretion to glucose in vitro.
• The study identified specific metabolic substrates and compounds that modulate insulin release from human islets.
• Findings provide insights into the regulation of insulin secretion by human islets, relevant for transplantation and diabetes research.