Gain of function of cardiac ryanodine receptor in a rat model of type 1 diabetes

Abstract

These data show, for the first time, that RyR2 is acquiring a gain-of-function phenotype independent of its phosphorylation status during T1D and provides new insights for the enhanced spontaneous Ca(2+) release in myocytes from T1D rats.

Carbonylation Induces Heterogeneity in Cardiac Ryanodine Receptor Function in Diabetes Mellitus

“…The induction of diabetes with STZ and the care of rats with type 1 diabetes were described in detail previously (Shao et al, 2009;Tian et al, 2011).…”

“…Western blots with membrane vesicles (30 g) were used to determine relative levels of RyR2 protein in hearts from control, diabetic, insulin-treated, and drug-treated animals Tian et al, 2011). Western blots with junctional sarcoplasmic reticulum vesicles (60 g), which were prepared by fractionating membrane vesicles on discontinuous sucrose gradients (Tian et al, 2011), were used to determine relative levels of argpyrimidine, N -carboxy(methyl)lysine, 3-deoxyglycosone/ hydroimidazolone, GA-pyridine, pentosidine, and pyrraline adducts with well characterized antibodies (Ling et al, 1998;Oya et al, 1999;Nagai et al, 2003Nagai et al, , 2008. ␤-Actin served as the internal control, to correct for variations in sample loading.…”

“…These paradoxical findings led us to propose the existence of two populations of RyR2s in diabetic myocytes, one population with enhanced Ca 2ϩ responsiveness and one with reduced Ca 2ϩ responsiveness (i.e., heterogeneity in RyR2 function in diabetes) (Shao et al, 2007). We purified dRyR2s under reducing and dephosphorylating conditions and, by using lipid bilayers, identified a population of channels with enhanced responsiveness to Ca 2ϩ , ATP, and cADP-ribose and reduced responsiveness to Mg 2ϩ (Tian et al, 2011). The population of RyR2s with reduced Ca 2ϩ responsiveness and the mechanisms responsible for heterogeneity in RyR2 function in diabetes remain to be characterized.…”

The effect of hexarelin in streptozotocin (STZ)-induced rat model through protective actions on islet beta cells and cardiomyocytes

“…Results showed characteristics of hyperglycemia, polyphagia, polydipsia and polyuria in STZ-treated diabetic rats, which was consistent with previously published studies [267][268][269]. As shown in Figure 3.1, the body weight gain of the STZ group was quite slow in comparison of control animals, whereas blood glucose level of STZ rats was dramatically increased and maintained at high levels through their life span, indicating apparent hyperglycemia presented in STZ-treated rats.…”

“…The STZ-induced animal model shows major characteristics of diabetes such as hyperglycemia, polyphagia, polydipsia and polyuria [267][268][269], and in my study, also presented increased blood glucose level, food intake, water consumption and urine production 44 in STZ-treated rats, consistent with diabetic patients.…”