Circadian rhythm in sensitivity of glucose metabolism to insulin in rat soleus muscle

Abstract

This study determined whether the sensitivity of glucose metabolism to insulin in skeletal muscle varies during a 24-h period. Soleus muscles were isolated from ad libitum-fed rats killed at 0900, 1600, 2100, and 0300. The animal house was illuminated between 0800 and 2000. The sensitivities of glycolysis (which is an excellent index of glucose transport) and glycogen synthesis to insulin were greatest in muscles isolated at 0900 and 2100. Marked decreases in sensitivities of both processes to insulin were observed in muscles isolated at 0300 and 1600, which are times halfway through the feeding and postabsorptive periods, respectively. Hence, this study demonstrates circadian changes in the sensitivity of glucose utilization by skeletal muscle to insulin, which may be important in control of blood glucose concentration. Glycogen levels in skeletal muscles were highest at 0300 and lowest at 2100; hepatic glycogen content reached a peak at 0900, and the lowest content was measured at 2100. The liver glycogen level was increased by only 15% midway into the feeding period (i.e., 0300). This suggests that muscle glycogen may act as a temporary store of glucose residues during the feeding period; it stores glycogen in the first half of the feeding period but during the second half some muscle glycogen is converted to lactate, which acts as a precursor for hepatic gluconeogenesis.

Evidence for altered sensitivity of the nitric oxide/cGMP signalling cascade in insulin-resistant skeletal muscle

“…Enzymes, chemicals, biochemicals and radiochemicals were purchased from sources listed previously [8,[18][19][20] except for Zaprinast (Sigma, Poole, Dorset, U.K.) and reagents for the NOS assay, such as [U-"%C]arginine from Amersham (Little Chalfont, Bucks., U.K.), calmodulin, flavin mononucleotide, PMSF and -arginine (Sigma). Leupeptin was purchased from Boehringer Mannheim (Germany).…”

“…Furthermore any difference between the rates of net and "%C-labelled lactate release probably indicates that glycogenolysis is activated in the isolated incubated soleus muscle. The rate of [U-"%C]glucose incorporation into glycogen was used to follow glycogen synthesis as described previously [18][19][20]24]. In other experiments the incubation medium was acidified with 6 % (w\v) HClO % before the collection of "%CO # in plastic centre wells containing 0.2 ml of phenylethylamine\methanol (1 : 1, v\v) [19].…”

Molecular and functional characterization of amylin, a peptide associated with type 2 diabetes mellitus.

“…Biological activities of synthetic and natural peptides were determined by measurement of insulin-stimulated rates of glycogen synthesis and lactate formation in the isolated incubated stripped soleus muscle of the rat, with materials and methods as previously described (13,14,27).…”

Circadian regulation of metabolism

“…Extra-hepatic tissues, such as muscle, contribute in a significant manner to glucose homeostasis. Diurnal variations in both skeletal and cardiac muscle glucose utilization persist ex vivo , suggesting that an intrinsic mechanism may contribute towards these rhythms (Leighton, et al 1988; Young, et al 2001a). In the case of the heart, genetic disruption of the cardiomyocyte circadian clock abolishes time-of-day-dependent rhythms in cardiac glucose oxidation, glycolysis, and glycogen synthesis, as well as protein O-GlcNAcylation (an indirect marker of flux through the hexosamine biosynthetic pathway) (Durgan et al 2011).…”