Substrate availability other than glucose in the brain during euglycemia and insulin-induced hypoglycemia in dogs

Abstract

Alternative substrates other than glucose could be used by the brain. In this study we hypothesized that lactate and ketone bodies can provide a significant portion of oxidative brain substrates in insulin-dependent diabetes mellitus (IDDM). Six control (C) and six insulin-treated streptozotocin diabetic (IDDM) dogs were studied during euglycemia (EU) and acute insulin induced hypoglycemia (HYPO). During EU for similar plasma glucose concentration (5.5 +/- 0.4 v 5.2 +/- 0.2 mmol/L in IDDM dogs showed a higher baseline lactate concentration (1.5 +/- 0.25 v 0.74 +/- 0.10 mmol/L; P less than .05). The ketone body concentrations were also increased in IDDM dogs but this increase was not statistically significant. The brain glucose uptake was 6.9 +/- 0.6 mumol/kg/min in C and 5.4 +/- 0.7 in IDDM. Lactate was released by the brain both in IDDM dogs (11.36 +/- 1.8 mumol/kg/min) and in C dogs (3.87 +/- 0.9; P less than .05). The brain ketones rate of disappearance (Rd) was 0.3 +/- 0.05 mumol/kg/min in IDDM dogs and 0.19 +/- 0.08 in C dogs. During HYPO the glucose uptake across the brain was 2.88 +/- 0.7 mumol/kg/min in IDDM and 3.12 +/- 0.5 in C dogs. We observed an overall brain lactate release (3.21 +/- 1.7 mol/kg/min) in C dogs and a net uptake (13.44 +/- 1.1; P less than .01) in IDDM (P less than .01). The brain ketones Rd was 0.1 +/- 0.2 mumol/kg/min in IDDM and 0.1 +/- 0.1 in C dogs.(ABSTRACT TRUNCATED AT 250 WORDS)