Ahrén B, Stern J S, Gingerich R L, Curry D L, Havel P J
Department of Medicine, Lund University, Malmö, Sweden.
Acta Physiol Scand. 1995 Oct;155(2):215-21. doi: 10.1111/j.1748-1716.1995.tb09966.x.
Glucagon response to insulin-induced hypoglycaemia is impared in diabetes, but the mechanism is not established. Pancreatic A cell hyporesponsiveness to adrenergic or cholinergic stimulation could contribute to the impairment. We therefore compared the plasma glucagon responses to intravenous infusion of adrenaline (1200 ng kg(-1) min(-1) for 20 min) or to intravenous injection of the cholinergic agonist carbachol (50 micrograms kg(-1)) in chloral hydrate-anaesthetized rats made diabetic with the use of streptozotocin (80 mg kg(-1) subcutaneously) 6 weeks before and in anaesthetized control rats. Insulin was infused intravenously to reduce plasma glucose levels to below 1.8 mmol L(-1). As expected, the plasma glucagon response was reduced by approximately 45% in streptozotocin-diabetic rats compared with controls (P = 0.045). During adrenaline infusion, plasma glucagon levels increased by 277 +/- 92 pg mL(-1) in controls (P = 0.009) and by 570 +/- 137 pg mL(-1) in the diabetic rats (P = 0.002). Thus, the plasma glucagon response to adrenaline was approximately doubled in the diabetic rats (P = 0.045). Following carbachol injection, plasma glucagon levels were raised by 1211 +/- 208 pg mL(-1) (P < 0.001) in controls but only by 555 +/- 242 pg mL(-1) in the diabetic rats (P = 0.049). Thus, the plasma glucagon response to carbachol was impared by approximately 58% in the diabetic rats (P = 0.028). We conclude that carbachol-stimulated glucagon secretion is impared concomitantly with the impared glucagon response to hypoglycaemia in streptozotocin-diabetic rats, whereas adrenaline-induced glucagon secretion is exaggerated. We suggest that a reduced pancreatic A cell responsiveness to cholinergic stimulation could contribute to the impairment of the glucagon response to insulin-induced hypoglycaemia in diabetes.
在糖尿病患者中，胰高血糖素对胰岛素诱导的低血糖的反应受损，但其机制尚未明确。胰岛A细胞对肾上腺素能或胆碱能刺激反应低下可能是导致这种损害的原因之一。因此，我们比较了在水合氯醛麻醉的大鼠中，静脉输注肾上腺素（1200 ng·kg⁻¹·min⁻¹，持续20分钟）或静脉注射胆碱能激动剂卡巴胆碱（50 μg·kg⁻¹）后血浆胰高血糖素的反应。这些大鼠在6周前皮下注射链脲佐菌素（80 mg·kg⁻¹）制成糖尿病模型，与麻醉的对照大鼠进行比较。静脉输注胰岛素使血浆葡萄糖水平降至1.8 mmol·L⁻¹以下。正如预期的那样，与对照组相比，链脲佐菌素诱导的糖尿病大鼠血浆胰高血糖素反应降低了约45%（P = 0.045）。在输注肾上腺素期间，对照组血浆胰高血糖素水平升高了277±92 pg·mL⁻¹（P = 0.009），糖尿病大鼠升高了570±137 pg·mL⁻¹（P = 0.002）。因此，糖尿病大鼠对肾上腺素的血浆胰高血糖素反应约增加了一倍（P = 0.045）。注射卡巴胆碱后，对照组血浆胰高血糖素水平升高了1211±208 pg·mL⁻¹（P < 0.001），而糖尿病大鼠仅升高了555±242 pg·mL⁻¹（P = 0.049）。因此，糖尿病大鼠对卡巴胆碱的血浆胰高血糖素反应受损约58%（P = 0.028）。我们得出结论，在链脲佐菌素诱导的糖尿病大鼠中，卡巴胆碱刺激的胰高血糖素分泌与胰高血糖素对低血糖的反应受损同时存在，而肾上腺素诱导的胰高血糖素分泌则被夸大。我们认为胰岛A细胞对胆碱能刺激反应性降低可能是糖尿病患者胰高血糖素对胰岛素诱导的低血糖反应受损的原因之一。
