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CART is overexpressed in human type 2 diabetic islets and inhibits glucagon secretion and increases insulin secretion

Mia Abels1, Matteo Riva1, Hedvig Bennet1

  • 1Lund University Diabetes Centre, Skåne University Hospital, Lund and Malmö, Sweden.

Diabetologia
|June 25, 2016
PubMed
Abstract

Insights

Cocaine- and amphetamine-regulated transcript (CART) is elevated in type 2 diabetes. CART enhances insulin secretion and reduces glucagon secretion, suggesting its potential as a diabetes therapy.

Area of Science:

  • Endocrinology
  • Metabolic Diseases
  • Molecular Biology

Background:

  • Type 2 diabetes is characterized by insufficient insulin release and excessive glucagon secretion.
  • Cocaine- and amphetamine-regulated transcript (CART) influences islet hormone secretion and beta cell survival.
  • CART knockout mice exhibit impaired insulin secretion.

Purpose of the Study:

  • To investigate differential regulation of CART in human type 2 diabetic islets.
  • To determine the effect of CART on insulin and glucagon secretion in human and mouse models.
  • To explore CART's role in glucose homeostasis and type 2 diabetes pathophysiology.

Main Methods:

  • Assessed CART expression in human diabetic and control pancreases and rodent diabetes models.
  • Examined insulin and glucagon secretion from isolated islets and in vivo in mice.
  • Studied calcium (Ca2+) oscillation patterns and exocytosis in mouse islets.

Main Results:

  • CART expression was significantly higher in type 2 diabetic human and rodent islets.
  • CART administration increased insulin secretion in vivo and in isolated islets.
  • CART reduced glucagon secretion and enhanced beta cell exocytosis, while altering Ca2+ signaling.
  • CART improved the synchronization of islet region oscillations.

Conclusions:

  • CART plays a crucial role in regulating glucose homeostasis.
  • Elevated CART expression in type 2 diabetes suggests its involvement in disease pathophysiology.
  • CART-based therapies hold potential for treating type 2 diabetes due to its insulin-enhancing and glucagon-reducing effects.
Keywords:
CART peptideCocaine- and amphetamine-regulated transcriptGlucagonInsulinIsletsType 2 diabetes

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