Open Accessp8 deficiency leads to elevated pancreatic beta cell mass but does not contribute to insulin resistance in mice fed with high-fat diet
Author(s) -
Marcus Hollenbach,
Nora Klöting,
Ines Sommerer,
Jana E. Lorenz,
Mario Heindl,
Matthias Kern,
Joachim Mössner,
Matthias Blüher,
Albrecht Hoffmeister
Publication year - 2018
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0201159
Subject(s) - medicine , endocrinology , insulin resistance , insulin , insulin tolerance test , glucagon , glucose tolerance test , glucose clamp technique , beta cell , impaired glucose tolerance , biology , type 2 diabetes , carbohydrate metabolism , glucose homeostasis , pancreatic hormone , diabetes mellitus , islet , insulin sensitivity
Background p8 was initially described as being overexpressed in acute pancreatitis and encoding a ubiquitous stress protein. Analysis of insulin sensitivity and glucose tolerance in p8-knockout and haplodeficient mice revealed counterintuitive results. Thus, we determined glycemic control of p8 in mice fed with standard (SD) and high-fat diet (HFD). Methods p8 -/- and wild type (p8 +/+ ) mice were used for analysis of glucagon (immunohistochemistry), insulin levels (ELISA) and beta cell mass. Hyperinsulinemic- euglycemic glucose clamp technique, i.p. glucose tolerance test (ipGTT), i.p. insulin tolerance test (ipITT) and metabolic chamber analysis were performed in SD (4% fat) and HFD (55% fat) groups. Results p8 -/- mice showed no differences in glucagon or insulin content but higher insulin secretion from pancreatic islets upon glucose stimulation. p8 deficiency resulted in elevated beta cell mass but was not associated with increased insulin resistance in ipGTT or ipITT. Glucose clamp tests also revealed no evidence of association of p8 deficiency with insulin resistance. Metabolic chamber analysis showed equal energy expenditure in p8 -/- mice and wild type animals. Conclusion p8 depletion may contribute to glucose metabolism via stress-induced insulin production and elevated beta cell mass. Nevertheless, p8 knockout showed no impact on insulin resistance in SD and HFD-fed mice.