Disturbed alpha-cell function in mice with beta-cell specific overexpression of human islet amyloid polypeptide.
Exogenous administration of islet amyloid polypeptide (IAPP) has been shown to inhibit both insulin and glucagon secretion. This study examined alpha-cell function in mice with beta-cell specific overexpression of human IAPP (hIAPP) after an oral protein gavage (75 mg whey protein/mouse). Baseline glucagon levels were higher in transgenic mice (41 +/- 4.0 pg/mL, n = 6) than in wildtype animals (19 +/- 5.1 pg/mL, n = 5, P = .015). In contrast, the glucagon response to protein was impaired in transgenic animals (21 +/- 2.7 pg/mL in transgenic mice versus 38 +/- 5.7 pg/mL in wildtype mice at 15 minutes; P = .027). Baseline insulin levels did not differ between the groups, while the insulin response, as the glucagon response, was impaired after protein challenge (P = .018). Glucose levels were not different between the groups and did not change significantly after protein gavage. Acetaminophen was given through gavage to the animals (2 mg/mouse) to estimate gastric emptying. The plasma acetaminophen profile was similar in the two groups of mice. We conclude that disturbances in glucagon secretion exist in mice with beta-cell specific overexpression of human IAPP, which are not secondary to changes in gastric emptying. The reduced glucagon response to protein challenge may reflect a direct inhibitory influence of hIAPP on glucagon secretion.
Ahrén
Bo
B
Department of Clinical Sciences, Lund University, 22184 Lund, Sweden. bo.ahren@med.lu.se
Sörhede Winzell
Maria
M
D000082:Acetaminophen / Q000097:blood / Q000494:pharmacology; D000284:Administration, Oral; D000682:Amyloid / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000032:analysis / Q000187:drug effects; D005260:Female; D005746:Gastric Emptying / Q000187:drug effects; D005934:Glucagon / Q000097:blood; D050416:Glucagon-Secreting Cells / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007328:Insulin / Q000097:blood; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism*; D058228:Islet Amyloid Polypeptide; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D009928:Organ Specificity / Q000235:genetics; D010182:Pancreatic Diseases / Q000097:blood / Q000209:etiology / Q000235:genetics*; D010186:Pancreatic Function Tests / Q000379:methods; D011506:Proteins / Q000008:administration & dosage; D015854:Up-Regulation / Q000235:genetics
D000682:Amyloid; D001786:Blood Glucose; D007328:Insulin; D058228:Islet Amyloid Polypeptide; D011506:Proteins; D000082:Acetaminophen; D005934:Glucagon