The emerging role of TRIB3 as a gene affecting human insulin resistance and related clinical outcomes.
Type 2 diabetes is becoming epidemic. The personal and social burden imposed by diabetes will increase in the close future as its prevalence is expected to double in the next 15-20 years. Type 2 diabetes is caused by the combination of resistance to insulin action and inadequate insulin secretion. Despite the role of profound changes in individual environmental exposure is incontrovertible, several findings clearly indicate that type 2 diabetes and insulin resistance are also heritable. Among the several inhibitors of insulin signalling, which have been recently proposed as determinants of insulin resistance, is TRIB3, a mammalian tribbles homolog which affects insulin signalling at the level of Akt-2, a key modulator of insulin action in target cells. We here report data on a prevalent Q84R TRIB3 missense single nucleotide polymorphism (rs2295490) we first described few years ago. Several lines of evidences indicate that this amino-acid change is, in fact, a gain of function mutation with the potential to affect insulin signalling and thus, to increase the risk of insulin resistance and related clinical outcomes.
Prudente
Sabrina
S
CSS-Mendel Institute, Viale Regina Margherita 261, 00198, Rome, Italy. s.prudente@css-mendel.it
Morini
Eleonora
E
Trischitta
Vincenzo
V
D019943:Amino Acid Substitution; D001120:Arginine; D018797:Cell Cycle Proteins / Q000235:genetics*; D017281:Cost of Illness; D003924:Diabetes Mellitus, Type 2 / Q000191:economics / Q000453:epidemiology / Q000235:genetics*; D014644:Genetic Variation; D005973:Glutamine; D006801:Humans; D015994:Incidence; D007328:Insulin / Q000502:physiology; D007333:Insulin Resistance / Q000235:genetics*; D020125:Mutation, Missense; D020641:Polymorphism, Single Nucleotide; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000037:antagonists & inhibitors; D012097:Repressor Proteins / Q000235:genetics*; D015398:Signal Transduction
D018797:Cell Cycle Proteins; D007328:Insulin; D012097:Repressor Proteins; C474831:TRIB3 protein, human; D005973:Glutamine; D001120:Arginine; D017346:Protein Serine-Threonine Kinases