The deletion of both IRS1 and insulin receptor substrate 2
(IRS2) (H-DKO mice: heart-specific IRS1 and IRS2 double gene knock-out) in the brain and liver causes hyperglycemia, but such deficiencies in the pancreas and heart cause organ failure .
Objective: To detect hepatic insulin receptor substrate 2
in chronic hepatitis C patients.
High insulin concentration in insulin resistance stimulates lipogenesis through the activation of sterol regulatory element-binding protein 1 (SREBP-1c) , which inhibits insulin receptor substrate 2
(IRS-2) mediated insulin signaling .
Insulin receptor substrate 2
is essential for maturation and survival of photoreceptor cells.
Variant E23K (rs5219) in KCNJ11, variants of the CDKAL1, variant rs10811661, rs4402960 in IGF2BP2 which lies near the CDKN2A gene, as well as polymorphisms in SLC30A8 and HHEX (identified by GWA studies) have been significantly associated with type 2 diabetes in Indians with an increased effect size compared with Europeans.[61,65] In Indians, the D1057D genotype of insulin receptor substrate 2
(IRS-2) gene is susceptible to diabetes by interacting with obesity , so as the genetic polymorphisms (Thr394Thr, Gly482Ser and +A2962G) of peroxisome proliferator activated receptor-coactivator-1 alpha (PGC-1) gene.
A novel link also was identified between the expression of A2bAR, insulin receptor substrate 2
(IRS-2) and insulin signaling.
Drugs that regulate insulin receptor substrate 2
(Irs2) signaling in the brain (but not elsewhere in the body) are one possible preventive strategy, but no such drug has yet been found.
Abbreviations: DMEM, Dulbecco modified eagle medium; GLUT-4, glucose transporter isotype 4; IRS-1, insulin receptor substrate 1; IRS-2, insulin receptor substrate 2
; IRC, insulin resistant cells; IL-6, interleukin-6; NCC, normal control cells; PBS, phosphate buffered saline; PCC, positive control cells; RP-HPLC, reverse phase high performance liquid chromatography; RNA, ribonucleic acid; RT-PCR, real time-polymerase chain reaction; THC, [[delta].sup.9]-tetrahydrocan-nabinol; TNF-[alpgha], tumour necrosis factor alpha; NIDDM, type 2 diabetes mellitus.
Insulin receptor substrate 2
plays a crucial role in [beta]cells and the hypothalamus.
Yet investigators who have engineered mice to lack a single gene--the one that encodes a protein called insulin receptor substrate 2
(IRS-2)--have found to their surprise that the animals display both of the main characteristics of type 2 diabetes.
Insulin signaling in peripheral neurons proceeds in a way analog to that in other cells, with successive phosphorylation of the insulin receptor itself, then the insulin receptor substrate 2
(IRS-2), phosphoinositide 3kinase (PI3K),phosphoinositide-dependentkinase-1 (PDK1), and subsequently protein kinase B (PKB/Akt) .
IR, insulin resistance/resistant; T2DM, type 2 diabetes mellitus; GK, Goto-Kakizaki; INSR, insulin receptor; IRS1, insulin receptor substrate 1; IRS2, insulin receptor substrate 2
; MAPK14, mitogen-activated protein kinase 14; AKT2, AKT serine/threonine kinase 2; PI3KR1, phosphoinositide-3-kinase regulatory subunit 1; MTOR, mechanistic target of rapamycin; RPS6KB1, ribosomal protein S6 kinase B1; RAC1, ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1).