STAT5 activity in pancreatic beta-cells influences the severity of diabetes in animal models of type 1 and 2 diabetes.

Malene Jackerott; Annette Møldrup; Peter Thams; Elisabeth D Galsgaard; Jakob Knudsen; Ying C Lee; Jens Høiriis Nielsen

doi:10.2337/db06-0244

STAT5 activity in pancreatic beta-cells influences the severity of diabetes in animal models of type 1 and 2 diabetes.

Malene Jackerott, Annette Møldrup, Peter Thams, Elisabeth D Galsgaard, Jakob Knudsen, Ying C Lee, Jens Høiriis Nielsen

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

48 Citationer (Scopus)

Abstract

Udgivelsesdato: 2006-Oct

Originalsprog	Engelsk
Tidsskrift	Diabetes
Vol/bind	55
Udgave nummer	10
Sider (fra-til)	2705-12
Antal sider	7
ISSN	0012-1797
DOI	https://doi.org/10.2337/db06-0244
Status	Udgivet - 2006

Bibliografisk note

Keywords: Animals; Blood Glucose; Cell Proliferation; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Dietary Fats; Glucose Tolerance Test; Insulin; Insulin-Secreting Cells; Leptin; Mice; Mice, Transgenic; STAT5 Transcription Factor

Adgang til dokumentet

10.2337/db06-0244

Citationsformater

STAT5 activity in pancreatic beta-cells influences the severity of diabetes in animal models of type 1 and 2 diabetes. / Jackerott, Malene; Møldrup, Annette; Thams, Peter; Galsgaard, Elisabeth D; Knudsen, Jakob; Lee, Ying C; Nielsen, Jens Høiriis.

I: Diabetes, Bind 55, Nr. 10, 2006, s. 2705-12.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

@article{f4d15f00acd011ddb538000ea68e967b,

title = "STAT5 activity in pancreatic beta-cells influences the severity of diabetes in animal models of type 1 and 2 diabetes.",

abstract = "Pancreatic beta-cell growth and survival and insulin production are stimulated by growth hormone and prolactin through activation of the transcription factor signal transducer and activator of transcription (STAT)5. To assess the role of STAT5 activity in beta-cells in vivo, we generated transgenic mice that expressed a dominant-negative mutant of STAT5a (DNSTAT5) or constitutive active mutant of STAT5b (CASTAT5) under control of the rat insulin 1 promoter (RIP). When subjected to a high-fat diet, RIP-DNSTAT5 mice showed higher body weight, increased plasma glucose levels, and impairment of glucose tolerance, whereas RIP-CASTAT5 mice were more glucose tolerant and less hyperleptinemic than wild-type mice. Although the pancreatic insulin content and relative beta-cell area were increased in high-fat diet-fed RIP-DNSTAT5 mice compared with wild-type or RIP-CASTAT5 mice, RIP-DNSTAT5 mice showed reduced beta-cell proliferation at 6 months of age. The inhibitory effect of high-fat diet or leptin on insulin secretion was diminished in isolated islets from RIP-DNSTAT5 mice compared with wild-type islets. Upon multiple low-dose streptozotocin treatment, RIP-DNSTAT5 mice exhibited higher plasma glucose levels, lower plasma insulin levels, and lower pancreatic insulin content than wild-type mice, whereas RIP-CASTAT5 mice maintained higher levels of plasma insulin. In conclusion, our results indicate that STAT5 activity in beta-cells influences the susceptibility to experimentally induced type 1 and type 2 diabetes.",

author = "Malene Jackerott and Annette M{\o}ldrup and Peter Thams and Galsgaard, {Elisabeth D} and Jakob Knudsen and Lee, {Ying C} and Nielsen, {Jens H{\o}iriis}",

note = "Keywords: Animals; Blood Glucose; Cell Proliferation; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Dietary Fats; Glucose Tolerance Test; Insulin; Insulin-Secreting Cells; Leptin; Mice; Mice, Transgenic; STAT5 Transcription Factor",

year = "2006",

doi = "10.2337/db06-0244",

language = "English",

volume = "55",

pages = "2705--12",

journal = "Diabetes",

issn = "0012-1797",

publisher = "American Diabetes Association",

number = "10",

}

TY - JOUR

T1 - STAT5 activity in pancreatic beta-cells influences the severity of diabetes in animal models of type 1 and 2 diabetes.

AU - Jackerott, Malene

AU - Møldrup, Annette

AU - Thams, Peter

AU - Galsgaard, Elisabeth D

AU - Knudsen, Jakob

AU - Lee, Ying C

AU - Nielsen, Jens Høiriis

N1 - Keywords: Animals; Blood Glucose; Cell Proliferation; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Dietary Fats; Glucose Tolerance Test; Insulin; Insulin-Secreting Cells; Leptin; Mice; Mice, Transgenic; STAT5 Transcription Factor

PY - 2006

Y1 - 2006

N2 - Pancreatic beta-cell growth and survival and insulin production are stimulated by growth hormone and prolactin through activation of the transcription factor signal transducer and activator of transcription (STAT)5. To assess the role of STAT5 activity in beta-cells in vivo, we generated transgenic mice that expressed a dominant-negative mutant of STAT5a (DNSTAT5) or constitutive active mutant of STAT5b (CASTAT5) under control of the rat insulin 1 promoter (RIP). When subjected to a high-fat diet, RIP-DNSTAT5 mice showed higher body weight, increased plasma glucose levels, and impairment of glucose tolerance, whereas RIP-CASTAT5 mice were more glucose tolerant and less hyperleptinemic than wild-type mice. Although the pancreatic insulin content and relative beta-cell area were increased in high-fat diet-fed RIP-DNSTAT5 mice compared with wild-type or RIP-CASTAT5 mice, RIP-DNSTAT5 mice showed reduced beta-cell proliferation at 6 months of age. The inhibitory effect of high-fat diet or leptin on insulin secretion was diminished in isolated islets from RIP-DNSTAT5 mice compared with wild-type islets. Upon multiple low-dose streptozotocin treatment, RIP-DNSTAT5 mice exhibited higher plasma glucose levels, lower plasma insulin levels, and lower pancreatic insulin content than wild-type mice, whereas RIP-CASTAT5 mice maintained higher levels of plasma insulin. In conclusion, our results indicate that STAT5 activity in beta-cells influences the susceptibility to experimentally induced type 1 and type 2 diabetes.

AB - Pancreatic beta-cell growth and survival and insulin production are stimulated by growth hormone and prolactin through activation of the transcription factor signal transducer and activator of transcription (STAT)5. To assess the role of STAT5 activity in beta-cells in vivo, we generated transgenic mice that expressed a dominant-negative mutant of STAT5a (DNSTAT5) or constitutive active mutant of STAT5b (CASTAT5) under control of the rat insulin 1 promoter (RIP). When subjected to a high-fat diet, RIP-DNSTAT5 mice showed higher body weight, increased plasma glucose levels, and impairment of glucose tolerance, whereas RIP-CASTAT5 mice were more glucose tolerant and less hyperleptinemic than wild-type mice. Although the pancreatic insulin content and relative beta-cell area were increased in high-fat diet-fed RIP-DNSTAT5 mice compared with wild-type or RIP-CASTAT5 mice, RIP-DNSTAT5 mice showed reduced beta-cell proliferation at 6 months of age. The inhibitory effect of high-fat diet or leptin on insulin secretion was diminished in isolated islets from RIP-DNSTAT5 mice compared with wild-type islets. Upon multiple low-dose streptozotocin treatment, RIP-DNSTAT5 mice exhibited higher plasma glucose levels, lower plasma insulin levels, and lower pancreatic insulin content than wild-type mice, whereas RIP-CASTAT5 mice maintained higher levels of plasma insulin. In conclusion, our results indicate that STAT5 activity in beta-cells influences the susceptibility to experimentally induced type 1 and type 2 diabetes.

U2 - 10.2337/db06-0244

DO - 10.2337/db06-0244

M3 - Journal article

C2 - 17003334

VL - 55

SP - 2705

EP - 2712

JO - Diabetes

JF - Diabetes

SN - 0012-1797

IS - 10

ER -