title: Tissue-specific ablation of Tsc1 in pancreatic beta-cells.
abstract: Tuberous sclerosis complex 1 (TSC1) is a tumor suppressor that associates with TSC2 to inactivate Rheb, thereby inhibiting signaling by the mammalian target of rapamycin (mTOR) complex 1 (mTORC1). mTORC1 stimulates cell growth by promoting anabolic cellular processes, such as translation, in response to growth factors and nutrient signals. In order to test roles for TSC1 and mTORC1 in β-cell function, we utilized Rip2/Cre to generate mice lacking Tsc1 in pancreatic β cells (Rip-Tsc1cKO mice). While obesity developed due to hypothalamic Tsc1 excision in older Rip-Tsc1cKO animals, young animals displayed a prominent gain-of-function β-cell phenotype prior to the onset of obesity. The young Rip-Tsc1cKO animals displayed improved glycemic control due to mTOR-mediated enhancement of β-cell size and insulin production, but not β-cell number consistent with an important anabolic role for mTOR in β-cell function. Thus, mTOR promulgates a dominant signal to promote β-cell/islet size and insulin production, and this pathway is crucial for β-cell function and glycemic control. Here, we describe the methods of analyzing tissue-specific ablation of Tsc1 in pancreatic β cells.
authors: Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, USA. morimori@umich.edu
authors: Hiroyuki
authors: H
authors: Mori
authors: Kun-Liang
authors: KL
authors: Guan
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D055786:Gene Knockout Techniques / Q000379:methods*; D006801:Humans; D007328:Insulin / Q000235:genetics / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D000076222:Mechanistic Target of Rapamycin Complex 1; D051379:Mice; D046912:Multiprotein Complexes; D011401:Promoter Regions, Genetic; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction; D020123:Sirolimus / Q000494:pharmacology; D058570:TOR Serine-Threonine Kinases; D014402:Tuberous Sclerosis / Q000235:genetics; D000077004:Tuberous Sclerosis Complex 1 Protein; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D007328:Insulin; D046912:Multiprotein Complexes; D011506:Proteins; C000624650:TSC1 protein, human; C000624651:Tsc1 protein, mouse; C000624652:Tsc1 protein, rat; D000077004:Tuberous Sclerosis Complex 1 Protein; D025521:Tumor Suppressor Proteins; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus