title: Disruption of protein-tyrosine phosphatase 1B expression in the pancreas affects β-cell function.
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 β-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.
authors: Nutrition Department (S.L., Y.X., A.B., K.M., I.M., F.G.H.), University of California Davis, Davis, California 95616; Joslin Diabetes Center (R.N.K.), Department of Medicine, Harvard Medical School, Boston, Massachusetts 02215; and Division of Endocrinology, Diabetes and Metabolism (F.G.H.), Department of Internal Medicine, and Comprehensive Cancer Center, University of California Davis, Sacramento, California 95817.
authors: Siming
authors: S
authors: Liu
authors: Yannan
authors: Y
authors: Xi
authors: Ahmed
authors: A
authors: Bettaieb
authors: Kosuke
authors: K
authors: Matsuo
authors: Izumi
authors: I
authors: Matsuo
authors: Rohit N
authors: RN
authors: Kulkarni
authors: Fawaz G
authors: FG
authors: Haj
mesh_terms: D000818:Animals; D005260:Female; D055786:Gene Knockout Techniques; D005947:Glucose / Q000378:metabolism; D018149:Glucose Intolerance; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000201:enzymology* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020799:Pancrelipase / Q000235:genetics / Q000378:metabolism; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000235:genetics* / Q000378:metabolism
chemical_list: D007328:Insulin; D020799:Pancrelipase; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D005947:Glucose