Hypothalamic-pituitary-adrenal response to different tests in type 1 diabetes mellitus

Objective: To determine whether different tests of the adrenocorticotropic hormone (ACTH) reserve are influenced by diabetic state and metabolic control in newly diagnosed type 1 diabetic patients. Design and methods: We evaluated the ACTH reserve in 10 patients with uncomplicated type 1 diabetes during periods of poor and improved metabolic control and in 10 healthy subjects. The ACTHcortisol secretion was assessed by a diurnal profile, an intravenous corticotropinreleasing hormone (CRH) test and an insulin tolerance test (ITT ). Results: The diurnal profiles were similar in all groups. CRH resulted in a diminished ACTH response during poor compared with improved metabolic control (mean &#45 SD) (AUC 4950 &#45 4227 vs. 5847 &#45 3788 ng/L·min, p< 0.05). The response in the diabetic patients during improved metabolic control was of the same magnitude as in the control subjects (5934 &#45 1778 ng/L·min). ITT elicited a similar ACTH and cortisol response in the diabetic patients during poor and improved metabolic control as in the healthy control subjects. Conclusions: The ITT was uninfluenced by diabetic state and metabolic control and should therefore be considered the method of choice in evaluation of the ACTH reserve in patients with type 1 diabetes.     

R-(α)-甲基组胺对AtT20垂体瘤细胞Pomc及其转录因子表达的影响

[目的]研究R-(α)-甲基组胺[R-(α)-MeHA]对AtT20垂体瘤细胞Pomc及其转录因子表达的影响.[方法]以小鼠垂体瘤细胞(AtT20)为实验对象,分别采用0.02～12.5μmol/L R-(α)-MeHA干预AtT20细胞24h,通过MTT检测药物对细胞增殖的影响;采用0.1μmol/LR-(α)-MeHA干预AtT20细胞30min、1、2、4、8、12h等相应时间,运用ELISA方法检测细胞分泌至培养液的促肾上腺皮质激素(ACTH)含量,RT-qPCR方法检测相关基因mRNA表达,Western blot方法检测相关蛋白表达.[结果] 0.02～12.5μmol/L的R-(α)-MeHA对AtT20细胞的增殖无抑制作用更无毒性作用.0.1μmol/R-(α)-MeHA对AtT20细胞ACTH分泌功能无明显作用.与对照组比较,0.1 μmol/L R-(α)-MeHA干预AtT20细胞4h后,可增强阿片促黑素皮质素原(Pomc)基因表达、0.5μmol/L R-(α)-MeHA促进Pomc蛋白表达;此外0.1μmol/L R-(α)-MeHA干预AtT20细胞30min～12h不同时点后Pou1f1基因表达均显著上调,其中以4h最为明显,上调达3倍(P＜0.05);同样,0.1 μmol/R-(α)-MeHA作用4h也显著促进Egr1基因表达上调约2倍(P＜0.05);作用1h显著增强了Prop1基因表达,上调近4倍(P＜0.05);干预4h、8h均显著上调Foxl2基因表达,上调约3倍(P＜0.05),对Neurod1、Pitx1和Tbx19基因表达无明显影响.[结论] R-(α)-MeHA具有促进Pomc基因以及其转录因子Pou1f1、Egr1、Prop1和Foxl2的表达作用.