Effects of delayed gastric emptying on postprandial glucose kinetics, insulin sensitivity, and β-cell function

Ling Hinshaw, Michele Schiavon, Ashwini Mallad, Chiara Dalla Man, Rita Basu, Adil E. Bharucha, Claudio Cobelli, Rickey E. Carter, Ananda Basu, Yogish C. Kudva

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Controlling meal-related glucose excursions continues to be a therapeutic challenge in diabetes mellitus. Mechanistic reasons for this need to be understood better to develop appropriate therapies. To investigate delayed gastric emptying effects on postprandial glucose turnover, insulin sensitivity, and β-cell responsivity and function, as a feasibility study prior to studying patients with type 1 diabetes, we used the triple tracer technique C-peptide and oral minimal model approach in healthy subjects. A single dose of 30 µg of pramlintide administered at the start of a mixed meal was used to delay gastric emptying rates. With delayed gastric emptying rates, peak rate of meal glucose appearance was delayed, and rate of endogenous glucose production (EGP) was lower. C-peptide and oral minimal models enabled the assessments of β-cell function, insulin sensitivity, and β-cell responsivity simultaneously. Delayed gastric emptying induced by pramlintide improved total insulin sensitivity and decreased total β-cell responsivity. However, β-cell function as measured by total disposition index did not change. The improved whole body insulin sensitivity coupled with lower rate of appearance of EGP with delayed gastric emptying provides experimental proof of the importance of evaluating pramlintide in artificial endocrine pancreas approaches to reduce postprandial blood glucose variability in patients with type 1 diabetes.

Original languageEnglish (US)
Pages (from-to)E494-E502
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume307
Issue number6
DOIs
StatePublished - Sep 15 2014

Keywords

  • Gastric emptying
  • Insulin action
  • Pramlintide

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

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