title: Postprandial lipemia induces pancreatic α cell dysfunction characteristic of type 2 diabetes: studies in healthy subjects, mouse pancreatic islets, and cultured pancreatic α cells.
abstract: BACKGROUND
  Type 2 diabetes is associated with pancreatic α cell dysfunction, characterized by elevated fasting plasma glucagon concentrations and inadequate postprandial glucose- and insulin-induced suppression of glucagon secretion. The cause and the underlying mechanisms of α cell dysfunction are unknown.
  
  
  OBJECTIVE
  Because Western dietary habits cause postprandial lipemia for a major part of a day and, moreover, increase the risk of developing type 2 diabetes, we tested the hypothesis that postprandial lipemia with its characteristic elevation of triglyceride-rich lipoproteins (TGRLs) might cause pancreatic α cell dysfunction.
  
  
  METHODS
  In a crossover study with 7 healthy volunteers, 2 experiments using 2 fat-enriched meals were performed on each volunteer; meal 1 was designed to increase plasma concentrations of both TGRLs and nonesterified fatty acids and meal 2 to increase TGRLs only. Intravenous glucose boli were injected at 0800 after an overnight fast and postprandially at 1300, 3 h after ingestion of a fat-enriched meal. Glucagon concentrations were measured throughout the days of the experiments. In addition to the study in humans, in vitro experiments were performed with mouse pancreatic islets and cultured pancreatic alpha TC 1 clone 9 (αTC1c9) cells, which were incubated with highly purified TGRLs.
  
  
  RESULTS
  In humans, postprandial lipemia increased plasma glucagon concentrations and led to an inadequate glucose- and insulin-induced suppression of glucagon. There was no difference between the 2 meal types. In mouse pancreatic islets and cultured pancreatic αTC1c9 cells, purified postprandial TGRLs induced abnormalities in glucagon kinetics comparable with those observed in humans. The TGRL-induced α cell dysfunction was due to reduced γ-aminobutyric acid A receptor activation in pancreatic α cells.
  
  
  CONCLUSIONS
  We concluded that postprandial lipemia induces pancreatic α cell dysfunction characteristic of type 2 diabetes and, therefore, propose that pancreatic α cell dysfunction could be viewed, at least partly, as a postprandial phenomenon.
authors.affiliation: From the Department of Internal Medicine I, Medical University of Innsbruck, Innsbruck, Austria (AN, CC, TT, MIK, RA-Z, KS, and MTP); KMT Laboratory, Department of Visceral, Transplant and Thoracic Surgery, Innsbruck Medical University, Innsbruck, Austria (MH); and the Clinical Department of Surgery, Hospital of Barmherzige Brüder, Salzburg, Austria (CM).
authors.forename: Andreas
authors.initials: A
authors.lastname: Niederwanger
authors.affiliation: From the Department of Internal Medicine I, Medical University of Innsbruck, Innsbruck, Austria (AN, CC, TT, MIK, RA-Z, KS, and MTP); KMT Laboratory, Department of Visceral, Transplant and Thoracic Surgery, Innsbruck Medical University, Innsbruck, Austria (MH); and the Clinical Department of Surgery, Hospital of Barmherzige Brüder, Salzburg, Austria (CM).
authors.forename: Christian
authors.initials: C
authors.lastname: Ciardi
authors.affiliation: From the Department of Internal Medicine I, Medical University of Innsbruck, Innsbruck, Austria (AN, CC, TT, MIK, RA-Z, KS, and MTP); KMT Laboratory, Department of Visceral, Transplant and Thoracic Surgery, Innsbruck Medical University, Innsbruck, Austria (MH); and the Clinical Department of Surgery, Hospital of Barmherzige Brüder, Salzburg, Austria (CM).
authors.forename: Tobias
authors.initials: T
authors.lastname: Tatarczyk
authors.affiliation: From the Department of Internal Medicine I, Medical University of Innsbruck, Innsbruck, Austria (AN, CC, TT, MIK, RA-Z, KS, and MTP); KMT Laboratory, Department of Visceral, Transplant and Thoracic Surgery, Innsbruck Medical University, Innsbruck, Austria (MH); and the Clinical Department of Surgery, Hospital of Barmherzige Brüder, Salzburg, Austria (CM).
authors.forename: Mohammad I
authors.initials: MI
authors.lastname: Khan
authors.affiliation: From the Department of Internal Medicine I, Medical University of Innsbruck, Innsbruck, Austria (AN, CC, TT, MIK, RA-Z, KS, and MTP); KMT Laboratory, Department of Visceral, Transplant and Thoracic Surgery, Innsbruck Medical University, Innsbruck, Austria (MH); and the Clinical Department of Surgery, Hospital of Barmherzige Brüder, Salzburg, Austria (CM).
authors.forename: Martin
authors.initials: M
authors.lastname: Hermann
authors.affiliation: From the Department of Internal Medicine I, Medical University of Innsbruck, Innsbruck, Austria (AN, CC, TT, MIK, RA-Z, KS, and MTP); KMT Laboratory, Department of Visceral, Transplant and Thoracic Surgery, Innsbruck Medical University, Innsbruck, Austria (MH); and the Clinical Department of Surgery, Hospital of Barmherzige Brüder, Salzburg, Austria (CM).
authors.forename: Christof
authors.initials: C
authors.lastname: Mittermair
authors.affiliation: From the Department of Internal Medicine I, Medical University of Innsbruck, Innsbruck, Austria (AN, CC, TT, MIK, RA-Z, KS, and MTP); KMT Laboratory, Department of Visceral, Transplant and Thoracic Surgery, Innsbruck Medical University, Innsbruck, Austria (MH); and the Clinical Department of Surgery, Hospital of Barmherzige Brüder, Salzburg, Austria (CM).
authors.forename: Ramona
authors.initials: R
authors.lastname: Al-Zoairy
authors.affiliation: From the Department of Internal Medicine I, Medical University of Innsbruck, Innsbruck, Austria (AN, CC, TT, MIK, RA-Z, KS, and MTP); KMT Laboratory, Department of Visceral, Transplant and Thoracic Surgery, Innsbruck Medical University, Innsbruck, Austria (MH); and the Clinical Department of Surgery, Hospital of Barmherzige Brüder, Salzburg, Austria (CM).
authors.forename: Karin
authors.initials: K
authors.lastname: Salzmann
authors.affiliation: From the Department of Internal Medicine I, Medical University of Innsbruck, Innsbruck, Austria (AN, CC, TT, MIK, RA-Z, KS, and MTP); KMT Laboratory, Department of Visceral, Transplant and Thoracic Surgery, Innsbruck Medical University, Innsbruck, Austria (MH); and the Clinical Department of Surgery, Hospital of Barmherzige Brüder, Salzburg, Austria (CM).
authors.forename: Michael T
authors.initials: MT
authors.lastname: Pedrini
mesh_terms: D000818:Animals; D008297:Male; D051379:Mice; D001786:Blood Glucose / Q000378:metabolism; D002470:Cell Survival; D002478:Cells, Cultured; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood; D059305:Diet, High-Fat / Q000009:adverse effects; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005934:Glucagon / Q000097:blood / Q000378:metabolism; D050416:Glucagon-Secreting Cells / Q000473:pathology; D064368:Healthy Volunteers; D006949:Hyperlipidemias / Q000097:blood; D007328:Insulin / Q000097:blood / Q000378:metabolism; D000078790:Insulin Secretion; D008074:Lipoproteins / Q000097:blood; D062407:Meals; D008810:Mice, Inbred C57BL; D019518:Postprandial Period / Q000502:physiology; D014280:Triglycerides / Q000097:blood; D006801:Humans
chemical_list: D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D005934:Glucagon; D007328:Insulin; C030087:lipoprotein triglyceride; D008074:Lipoproteins; D014280:Triglycerides