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Prolonged GIP receptor activation using stable mini-PEGylated GIP improves glucose homeostasis and beta-cell function in age-related glucose intolerance.

Abstract
In older populations there is significant increase in incidence of impaired glucose tolerance and diabetes. Glucose-dependent insulinotropic polypeptide (GIP) improves glycemic control but its use as a therapeutic is hindered by short biological half-life. The present study examined effects of a longer-acting form of GIP, GIP[mPEG], on glucose homeostasis and beta-cell function in mice with age-related glucose intolerance. GIP[mPEG] decreased glucose and increased insulin concentrations when administered prior to a glucose challenge. Daily administration of GIP[mPEG] for 20 days had no effect on body weight and food intake. However, non-fasting glucose concentrations were decreased and insulin concentrations increased. Glycemic response to intraperitoneal glucose was improved and glucose-mediated insulin secretion enhanced. Insulin sensitivity, circulating triglycerides and resistin levels were unchanged by the treatment regimen, but plasma adiponectin levels increased. These data indicate that prolonged activation of the GIP receptor with GIP[mPEG] counters aspects of impaired beta-cell function and age-related glucose intolerance.
AuthorsBarry D Kerr, Nigel Irwin, Peter R Flatt, Victor A Gault
JournalPeptides (Peptides) Vol. 30 Issue 2 Pg. 219-25 (Feb 2009) ISSN: 0196-9781 [Print] United States
PMID19026698 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Adiponectin
  • Blood Glucose
  • Incretins
  • Receptors, Gastrointestinal Hormone
  • Resistin
  • Triglycerides
  • Polyethylene Glycols
  • Gastric Inhibitory Polypeptide
  • gastric inhibitory polypeptide receptor
Topics
  • Adiponectin (blood)
  • Animals
  • Blood Glucose (drug effects, metabolism)
  • Body Weight
  • Eating
  • Gastric Inhibitory Polypeptide (chemistry, pharmacology)
  • Glucose Intolerance (metabolism)
  • Incretins (chemistry, pharmacology)
  • Insulin-Secreting Cells (metabolism)
  • Male
  • Mice
  • Polyethylene Glycols (chemistry)
  • Receptors, Gastrointestinal Hormone (metabolism)
  • Resistin (blood)
  • Triglycerides (blood)

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