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Publication
Disruption of protein-tyrosine phosphatase 1B expression in the pancreas affects
ß-cell function.
Authors Liu S, Xi Y, Bettaieb A, Matsuo K, Matsuo I, Kulkarni RN, Haj FG
Submitted By Submitted Externally on 11/3/2015
Status Published
Journal Endocrinology
Year 2014
Date Published 9/1/2014
Volume : Pages 155 : 3329 - 38
PubMed Reference 24956127
Abstract Protein-tyrosine phosphatase 1B (PTP1B) is a physiological regulator of glucose
homeostasis and energy balance. However, the role of PTP1B in pancreatic
endocrine function remains largely unknown. To investigate the metabolic role of
pancreatic PTP1B, we generated mice with pancreas PTP1B deletion (panc-PTP1B
KO). Mice were fed regular chow or a high-fat diet, and metabolic parameters,
insulin secretion and glucose tolerance were determined. On regular chow,
panc-PTP1B KO and control mice exhibited comparable glucose tolerance whereas
aged panc-PTP1B KO exhibited mild glucose intolerance. Furthermore, high-fat
feeding promoted earlier impairment of glucose tolerance and attenuated
glucose-stimulated insulin secretion in panc-PTP1B KO mice. The secretory defect
in glucose-stimulated insulin secretion was recapitulated in primary islets ex
vivo, suggesting that the effects were likely cell-autonomous. At the molecular
level, PTP1B deficiency in vivo enhanced basal and glucose-stimulated tyrosyl
phosphorylation of EphA5 in islets. Consistently, PTP1B overexpression in the
glucose-responsive MIN6 ß-cell line attenuated EphA5 tyrosyl phosphorylation,
and substrate trapping identified EphA5 as a PTP1B substrate. In summary, these
studies identify a novel role for PTP1B in pancreatic endocrine function.




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