Evolution of Prediabetic Condition in Aged Mice Lacking Functional Gabab Receptors

MARTIN CRIVELLO; MARIA MARTA BONAVENTURA; BERNHARD BETTLER; CARLOS LIBERTUN; VICTORIA ADELA LUX-LANTOS.

Chicago, ILL.

Congreso; The Endocrine Society (USA). 96th Annual Meeting and XVI International Congress of Endocrinology.; 2014

The Endocrine Society (USA).

Abstract #13967 Evolution of Prediabetic Condition in Aged Mice Lacking Functional Gabab Receptors Martin Crivello, MSc1, Maria Marta Bonaventura, PhD1, Bernhard Bettler, PhD2, Carlos Libertun, MD, PhD1 and Victoria Adela Lux-Lantos, PhD1, (1)Neuroendocrinology, Instituto de Biologia y Medicina Experimental-CONICET, Buenos Aires, Argentina, (2)Dept of Biomedicine, Univ. of Basel, Basel, Switzerland During the past years the role of GABA in endocrine pancreas function has emerged as an increasingly active area of study. Previously, we demonstrated adult GABAB-receptor knock-out mice (GABABKO) to suffer disruptions in glucose homeostasis (1-3). As insulin resistance increases with age, here we followed survival and glucose homeostasis parameters in 7-11 month old male and female GABABKO and WT mice. We found no differences in body weight, fasting serum insulin or the HOMA insulin-resistance index (HOMA-IR) among groups at 200, 250 or 300 days, while we had detected an increase in the later two parameters in young adult GABABKO males. No differences were found in fasting glucose in male mice; females had higher blood glucose at 250 and 300 days vs. 200 days (p<0.03), irrespective of genotype. At 300 days, GABABKO males had impaired glucose tolerance compared to WT [blood glucose at 45 min post glucose overload (2 g/kg ip): WT-males: 138±13 vs GABABKO-males: 184±26, p<0.05], something we had found occurs in young male adults only after a higher glucose challenge (3g/kg); no differences in glucose tolerance were found in females. Nevertheless, GABABKO females had a decreased survival rate (60%) compared to WTs (90%) at 300 days, p<0.05; glucose metabolism did not seem to be the cause of increased mortality. These results show that GABABKO males have worsened their glucose tolerance with age, but not their HOMA-IR. Unlike their younger counterparts, old WT females did not differ from GABABKOs in the glucose homeostasis parameters measured. We propose this may occur due to WT females entering reproductive senescence. In addition, aged GABABKO females have an increased mortality rate, unrelated to glucose metabolism.