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PLoS One. 2018 Jul 24;13(7):e0201159. doi: 10.1371/journal.pone.0201159. eCollection 2018.

p8 deficiency leads to elevated pancreatic beta cell mass but does not contribute to insulin resistance in mice fed with high-fat diet.

Author information

1
Department of Medicine, Neurology and Dermatology, Division of Gastroenterology and Rheumatology, University of Leipzig, Leipzig, Germany.
2
IFB Adiposity Disease, University of Leipzig, Leipzig, Germany.
3
German Diabetes Center Leipzig, University of Leipzig, Leipzig, Germany.
4
Department of Medicine, Neurology and Dermatology, Division of Endocrinology and Nephrology, University of Leipzig, Leipzig, Germany.

Abstract

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.

PMID:
30040846
PMCID:
PMC6057664
DOI:
10.1371/journal.pone.0201159
[Indexed for MEDLINE]
Free PMC Article

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