Loss of Pulsatile Insulin Secretion: A Factor in the Pathogenesis of Type 2 Diabetes?

  1. Åsa Kallas2
  1. 1Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
  2. 2Cebix AB, Karolinska Institutet Science Park, Solna, Sweden
  1. Corresponding author: John Wahren, john.wahren{at}ki.se.

For many years, the prevailing view has been that the initiating event in type 2 diabetes is development of insulin resistance in peripheral tissues that triggers overproduction of insulin by pancreatic β-cells. Eventually, β-cells reach a stage at which they are unable to compensate for the insulin resistance, resulting in hyperglycemia and overt diabetes. The underlying cause of tissue insulin resistance is not well understood, but several putative mechanisms including ectopic lipid accumulation and low-grade activation of inflammatory pathways have been proposed (1). Recent evidence suggests that β-cell failure may occur in parallel with the development of insulin resistance (2), and β-cell failure may in itself be a cause of insulin resistance (3).

Insulin is secreted into the portal vein in a pulsatile fashion with approximately 5-min cycles (Fig. 1) (46). Insulin pulses may account for as much as 70% of the total insulin secretion in the basal state (4). This pulsatile β-cell secretion pattern is controlled by an intrinsic rhythm of intracellular Ca2+ oscillations (7). Adjacent β-cells in the islets adapt to each other via autocrine interaction, resulting in a coordinated secretion pattern. In addition, synchronization of all islets so that insulin release by the entire pancreas occurs in distinct peaks results from autonomic …

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