RESUMO
AIMS/HYPOTHESIS: Acute hyperglycaemia rapidly suppresses endogenous glucose production (EGP) in non-diabetic individuals, mainly by inhibiting glycogenolysis. Loss of this 'glucose effectiveness' contributes to fasting hyperglycaemia in type 2 diabetes. Elevated NEFA levels characteristic of type 2 diabetes impair glucose effectiveness, although the mechanism is not fully understood. Therefore we examined the impact of increasing NEFA levels on the ability of hyperglycaemia to regulate pathways of EGP. METHODS: We performed 4 h 'pancreatic clamp' studies (somatostatin; basal glucagon/growth hormone/insulin) in seven non-diabetic individuals. Glucose fluxes (D-[6,6-(2)H(2)]glucose) and hepatic glycogen concentrations ((13)C magnetic resonance spectroscopy) were quantified under three conditions: euglycaemia, hyperglycaemia and hyperglycaemia with elevated NEFA (HY-NEFA). RESULTS: EGP was suppressed by hyperglycaemia, but not by HY-NEFA. Hepatic glycogen concentration decreased ~14% with prolonged fasting during euglycaemia and increased by ~12% with hyperglycaemia. In contrast, raising NEFA levels in HY-NEFA caused a substantial ~23% reduction in hepatic glycogen concentration. Moreover, rates of gluconeogenesis were decreased with hyperglycaemia, but increased with HY-NEFA. CONCLUSIONS/INTERPRETATION: Increased NEFA appear to profoundly blunt the ability of hyperglycaemia to inhibit net glycogenolysis under basal hormonal conditions.
Assuntos
Glicemia/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Ácidos Graxos não Esterificados/sangue , Glicogenólise/fisiologia , Hiperglicemia/metabolismo , Adulto , Jejum/fisiologia , Glucagon/sangue , Técnica Clamp de Glucose/métodos , Glicogênio/metabolismo , Hormônio do Crescimento Humano/sangue , Humanos , Insulina/sangue , Fígado/metabolismo , Masculino , Somatostatina/sangueRESUMO
An apparatus and a method for rapidly determining chemical toxicity have been evaluated as an alternative to the rabbit eye initancy test (Draize). The toxicity monitor includes an automated scoring of how motile biological cells (Tetrahymena pyriformis) slow down or otherwise change their swimming patterns in a hostile chemical environment. The method, called the Motility Assay (MA), is tested for 30 s to determine the chemical toxicity in 20 aqueous samples containing trace organics and salts. With equal or better detection limits, results compare favorably to in vivo animal tests of eye irritancy.