Giaccari A, Morviducci L, Pastore L, Zorretta D, Sbraccia P, Maroccia E, Buongiorno A, Tamburrano G
Institute of Endocrinology, Catholic University, Rome, Italy.
Diabetologia. 1998 Mar;41(3):307-14. doi: 10.1007/s001250050908.
Several studies have suggested that, in non-insulin-dependent diabetes mellitus, augmented gluconeogenesis is responsible for increased endogenous glucose production (EGP) and in the end determines fasting hyperglycaemia. However, human and animal studies have been conducted by comparing euglycaemic control subjects to hyperglycaemic diabetic probands. We measured EGP and hepatic gluconeogenesis comparing control and diabetic rats in the fasting state (with diabetic animals in hyperglycaemia), re-examining them in the presence of identical euglycaemia (with diabetic rats made acutely euglycaemic through i. v. phloridzin) or during a hyperinsulinaemic clamp. All rats were infused with [3-3H]-glucose and [U-14C]-lactate; the ratio between 14C-uridine-diphosphoglucose (reflecting 14C-glucose 6-phosphate) and 2 14C-phosphoenolpyruvate specific activities (both purified by high performance liquid chromatography from liver) measured hepatic gluconeogenesis. In diabetic animals, although overall EGP ( approximately 19.5 mg x kg[-1] x min[-1]) remained unaffected by experimental euglycaemia, the contribution of glycogenolysis largely increased (from 5.4 to 11.7 mg x kg(-1) min(-1), hyper- vs euglycaemia) while gluconeogenesis decreased (from 14.0 to 8.1 mg x kg(-1) x min[-1]); both were responsible for the augmented EGP (control rats, EGP: 12.7 mg x kg(-1) x min(-1); gluconeogenesis: 5.9 mg x kg(-1) x min(-1); glycogenolysis: 6.7 mg x kg[-1] x min[-1]). Finally, during insulin clamp, gluconeogenesis and glycogenolysis were similarly decreased, and both contributed to the hepatic insulin-resistance of diabetic animals. We conclude that, in this model of non-insulin-dependent diabetes, augmented gluconeogenesis is not primarily responsible for fasting hyperglycaemia and hepatic insulin resistance. Finally, failure to accurately match the experimental conditions in which diabetic and control humans or animals are compared affects gluconeogenesis, overestimating its role in determining hyperglycaemia.
多项研究表明，在非胰岛素依赖型糖尿病中，糖异生增强是内源性葡萄糖生成（EGP）增加的原因，最终导致空腹血糖升高。然而，以往的人体和动物研究都是将血糖正常的对照受试者与血糖升高的糖尿病先证者进行比较。我们通过比较空腹状态下的对照大鼠和糖尿病大鼠（糖尿病动物处于高血糖状态）来测量EGP和肝糖异生，在相同血糖水平下（通过静脉注射根皮苷使糖尿病大鼠急性血糖正常）或在高胰岛素钳夹期间再次检测它们。所有大鼠均输注[3-3H] -葡萄糖和[U-14C] -乳酸；通过高效液相色谱法从肝脏中纯化得到的14C-尿苷二磷酸葡萄糖（反映14C-葡萄糖6-磷酸）与2种14C-磷酸烯醇丙酮酸比活性之间的比值用于测量肝糖异生。在糖尿病动物中，尽管总体EGP（约19.5 mg·kg-1·min-1）不受实验性血糖正常的影响，但糖原分解的贡献大幅增加（从5.4增至11.7 mg·kg-1·min-1，高血糖与血糖正常相比），而糖异生则减少（从14.0降至8.1 mg·kg-1·min-1）；两者共同导致了EGP的增加（对照大鼠，EGP：12.7 mg·kg-1·min-1；糖异生：5.9 mg·kg-1·min-1；糖原分解：6.7 mg·kg-1·min-1）。最后，在胰岛素钳夹期间，糖异生和糖原分解同样减少，两者都导致了糖尿病动物的肝脏胰岛素抵抗。我们得出结论，在这种非胰岛素依赖型糖尿病模型中，糖异生增强并非空腹血糖升高和肝脏胰岛素抵抗的主要原因。最后，在比较糖尿病和对照人类或动物时，未能准确匹配实验条件会影响糖异生，高估其在决定高血糖中的作用。
