Exercise‐Induced Increase in Pro‐ and Macroglycogen Content in Hearts from Type 1 Diabetic Mice

Abstract

Diabetes adversely affects glucose metabolism, resulting in elevated levels of heart glycogen. Exercise training increases glycogen synthesis activity in diabetes; therefore the aim of this study was to examine the effects of exercise on glycogen content in hearts from streptozotocin-induced (insulin-deficient for duration of study) type 1 diabetic mice (T1D) mice compared to CD-1 controls. Mice were exercised by running for 60 min/d, 5 d/wk for 6 wk at low-moderate intensity. Hearts from T1D and control mice at 12 wk of age were subjected to a 60 min working heart perfusion with glucose and palmitate, prior to glycogen measurements (μmol/g dw) as total glycogen (Gt), proglycogen (PG) and macroglycogen (MG). Gt for T1D sedentary (SED) hearts was not significantly different from SED or exercised (EX) non-diabetic, CD1 controls. In T1D SED hearts, PG contributed 60% of total glycogen, which was significantly elevated compared to EX controls but not to SED controls. EX T1D hearts showed a nearly 2-fold increase in Gt compared to SED diabetic hearts (935±86 vs 584±20) with PG and MG contributing 558±21 and 436±80 glucosyl units respectively. There are intriguing aspects of this data: i) there was no difference in Gt between SED T1D and controls implying glycogen synthesis is not impaired in T1D hearts. (ii) Elevated PG levels in T1D hearts reflects a distinct selective process in glycogen formation compared to controls, suggesting T1D hearts form new granules at the expense of MG to maintain Gt. (iii) An exercise-induced improvement in glucose disposal may account for elevated PG and MG levels in EX T1D perfused hearts. Supported by CIHR (DS) and Genome Alberta (JS).