title: Amylin effect in extrapancreatic tissues participating in glucose homeostasis, in normal, insulin-resistant and type 2 diabetic state.
abstract: Amylin is co-secreted with insulin, responds to the same stimuli, is anorectic, lowers body weight by reducing fat mass, and is proposed for diabetes treatment. We examined the effect of a 3-day constant infusion of close to physiological doses of amylin in Wistar rats, on glucotransporter expression, glycogen content (G), glycogen synthase a activity (GSa) and glucose transport (GT), in liver, muscle and fat from insulin resistant (IR) and type 2 diabetic (T2D) models, compared to normal (N) animals; plasma glucose and insulin were measured. Plasma insulin in IR was higher than in N or T2D, and amylin normalized the value. In both, IR and T2D, liver G was lower than normal, accompanied by GLUT-2, mRNA and protein, higher and lower, respectively, than in N; amylin normalized G in both groups, without changes in GLUT-2, except for an mRNA increase in T2D. In IR and T2D, muscle GSa was reduced, together with respective over- and under-GLUT-4 expression; amylin induced only a trend toward GSa normalization in both groups. In isolated adipocytes, GT and GLUT-4 in IR and T2D were lower and higher, respectively, than in N; after amylin, not only GT was normalized in both groups but also the response to insulin was much more pronounced, including that in N, without major changes in GLUT-4. This suggests that the beneficial effect of amylin in states running with altered glucose homeostasis could occur by partially acting on the hexose metabolism of the liver and mainly on that of the adipose tissue.
authors.affiliation: Departamento Metabolism, Nutrition & Hormones, IIS-Fundación Jiménez Díaz, Madrid, Spain.
authors.forename: P
authors.initials: P
authors.lastname: Moreno
authors.forename: A
authors.initials: A
authors.lastname: Acitores
authors.forename: I
authors.initials: I
authors.lastname: Gutiérrez-Rojas
authors.forename: B
authors.initials: B
authors.lastname: Nuche-Berenguer
authors.forename: M
authors.initials: M
authors.lastname: El Assar
authors.forename: L
authors.initials: L
authors.lastname: Rodriguez-Mañas
authors.forename: R
authors.initials: R
authors.lastname: Gomis
authors.forename: I
authors.initials: I
authors.lastname: Valverde
authors.forename: M
authors.initials: M
authors.lastname: Visa
authors.forename: W J
authors.initials: WJ
authors.lastname: Malaisse
authors.forename: A
authors.initials: A
authors.lastname: Novials
authors.forename: N
authors.initials: N
authors.lastname: González
authors.forename: M L
authors.initials: ML
authors.lastname: Villanueva-Peñacarrillo
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D051273:Glucose Transporter Type 2 / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D006006:Glycogen Synthase / Q000378:metabolism; D006706:Homeostasis / Q000187:drug effects*; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology*; D058228:Islet Amyloid Polypeptide / Q000097:blood / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar
chemical_list: D001786:Blood Glucose; D051273:Glucose Transporter Type 2; D051275:Glucose Transporter Type 4; D007328:Insulin; D058228:Islet Amyloid Polypeptide; D006003:Glycogen; D006006:Glycogen Synthase