NEUROTRANSMITTER REGULATION OF INSULIN SECRETION IN HUMAN ISLETS OF LANGERHANS

• Author / Creator

  YAN-DO, RICHARD

• Insulin is secreted from pancreatic islet β-cells and impaired insulin secretion is a hallmark of practically all forms of diabetes. The release of insulin from pancreatic β-cells is regulated electrically, chemically, and hormonally; and loss of regulation may lead to disease. There is evidence that islets are modulated by classical neurotransmitters which control intracellular Ca2+ levels, excitability, and hormone secretion. Pancreatic islets express a variety of receptors (e.g. adrenergic, muscarinic, glutamatergic, GABAergic, purinergic, serotonergic) and each receptor has a different mechanism to regulate islet function and insulin secretion.
  In this thesis paracrine and autocrine neurotransmitter regulation, by purinergic receptors and glycinergic receptors, of human islet β-cells are investigated and the mechanism of action is studied. This work presents evidence that P2Y1 receptors regulate β-cell activity and insulin secretion and that ATP acts as a paracrine signal in a feed forward loop to further enhance insulin secretion.
  The work presented here also demonstrates the expression and the mechanism of action of glycine receptors in human β-cells. Evidence that glycine is secreted from β-cells, activates glycine receptors to increase intracellular Ca2+, and stimulates insulin secretion is demonstrated. The important role of glycine as an autocrine/paracrine signal is also investigated in intact human islets. Network activity and the connectivity of regions within the islet was demonstrated to be impaired by pharmacological inhibition of glycinergic receptors.
  Finally, this thesis also describes a loss of neurotransmitter signaling (both by ATP and glycine) in type 2 diabetes consistent with the idea that autocrine signaling may become impaired in this disease state.

• Subjects / Keywords

  • ISLETS OF LANGERHANS
  • INSULIN
  • TYPE 2 DIABETES

• Graduation date

  Fall 2019

• Type of Item

  Thesis

• Degree

  Doctor of Philosophy

• DOI

  https://doi.org/10.7939/r3-dew6-7w96

• License

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