title: Increased insulin secretion and glucose tolerance in mice lacking islet amyloid polypeptide (amylin).
abstract: Islet amyloid polypeptide (IAPP or amylin) is costored and cosecreted with insulin and may regulate insulin secretion and blood glucose handling. However, the role and importance of endogenous IAPP in the regulation of insulin release and glucose homeostasis have been controversial. Here we report on the generation and phenotypic analysis of IAPP-deficient mice. These mice have normal, or near to normal, basal levels of circulating insulin and glucose. However, following glucose administration, IAPP-deficient males presented increased insulin responses paralleled with a more rapid blood glucose elimination compared to wild-type controls. Blood glucose elimination was also found to be enhanced in IAPP-deficient females, but the insulin response in this gender did not differ from controls. In a transgenic rescue experiment, using an insulin-promoter human-IAPP fusion gene, insulin responses and blood glucose elimination were reversed in IAPP-deficient males, whereas the female phenotype appeared unaffected. Our results provide the first firm evidence of a physiological role for endogenous IAPP and indicate that IAPP, apparently in a gender-dependent manner, limits the degree of glucose-induced insulin secretion and the rate of blood glucose elimination.
authors.affiliation: Department of Medical Biochemistry, Göteborg University, Sweden. samuel.gebre-medhin@medkem.gu.se
authors.forename: S
authors.initials: S
authors.lastname: Gebre-Medhin
authors.forename: H
authors.initials: H
authors.lastname: Mulder
authors.forename: M
authors.initials: M
authors.lastname: Pekny
authors.forename: G
authors.initials: G
authors.lastname: Westermark
authors.forename: J
authors.initials: J
authors.lastname: Törnell
authors.forename: P
authors.initials: P
authors.lastname: Westermark
authors.forename: F
authors.initials: F
authors.lastname: Sundler
authors.forename: B
authors.initials: B
authors.lastname: Ahrén
authors.forename: C
authors.initials: C
authors.lastname: Betsholtz
mesh_terms: D000682:Amyloid / Q000172:deficiency* / Q000235:genetics; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D005260:Female; D017353:Gene Deletion; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D058228:Islet Amyloid Polypeptide; D008297:Male; D051379:Mice; D051381:Rats; D012737:Sex Factors
chemical_list: D000682:Amyloid; D001786:Blood Glucose; D007328:Insulin; D058228:Islet Amyloid Polypeptide