Lechin Fuad, van der Dijs Bertha
Department of Physiological Sciences, Sections of Neurochemistry, Neurophysiology, Neuroimmunology and Neuropharmacology, Instituto de Medicina Experimental, Universidad Central de Venezuela, Caracas, Venezuela.
Neuroendocrinology. 2006;84(4):222-34. doi: 10.1159/000098005. Epub 2006 Dec 12.
Raised plasma levels of insulin, glucose and glucagon are found in patients affected by 'hyperinsulinism'. Obesity, hypertension, mammary plus ovary cysts and rheumatic symptoms are frequently observed in these patients. Sleep disorders and depression are also present in most subjects affected by this polysymptomatic disorder. The simultaneous increases of glucose, insulin and glucagon plasma levels seen in these patients indicate that the normal crosstalk between A cells, B cells and D cells is disrupted. With respect to this, it is well known that glucose excites B cells (which secrete insulin) and inhibits A cells (which secrete glucagon), which in turn excites D cells (which secrete somatostatin). Gastrointestinal hormones (incretins) modulate this crosstalk both directly and indirectly throughout pancreatic and hepatobiliary mechanisms. The above factors depend on autonomic nervous system mediation. For instance, acetylcholine released from parasympathetic nerves excites both B and A cells. Noradrenaline released from sympathetic nerves and adrenaline secreted from the adrenal glands inhibit B cells and excite A cells, which are crowded with beta(2)- and alpha(2)-receptors, respectively. Noradrenaline released from sympathetic nerves also excites A cells by acting at alpha(1)-receptors located at this level. According to this, the excessive release of noradrenaline from these nerves should provoke an enhancement of glucagon secretion which will result in overexcitation of insulin secretion from B cells. That is the disorder seen in the so-called 'hyperinsulinism', in which raised plasma levels of glucose, insulin and glucagon coexist. Taking into account that neural sympathetic activity is positively correlated to the A5 noradrenergic nucleus and median raphe serotonergic neurons, and negatively correlated to the A6 noradrenergic, the dorsal raphe serotonergic and the C1 adrenergic neurons, we postulate that this unbalanced central nervous system circuitry is responsible for the hyperinsulinism syndrome.
“高胰岛素血症”患者的血浆胰岛素、葡萄糖和胰高血糖素水平升高。这些患者常出现肥胖、高血压、乳腺及卵巢囊肿和风湿症状。大多数患有这种多症状疾病的患者还存在睡眠障碍和抑郁症。这些患者中同时出现的葡萄糖、胰岛素和胰高血糖素血浆水平升高表明A细胞、B细胞和D细胞之间的正常相互作用被破坏。关于这一点，众所周知，葡萄糖刺激B细胞（分泌胰岛素）并抑制A细胞（分泌胰高血糖素），而A细胞又刺激D细胞（分泌生长抑素）。胃肠激素（肠促胰岛素）通过胰腺和肝胆机制直接或间接调节这种相互作用。上述因素依赖于自主神经系统的介导。例如，副交感神经释放的乙酰胆碱刺激B细胞和A细胞。交感神经释放的去甲肾上腺素和肾上腺分泌的肾上腺素抑制B细胞并刺激A细胞，A细胞分别富含β(2) -和α(2) -受体。交感神经释放的去甲肾上腺素也通过作用于该水平的α(1) -受体来刺激A细胞。据此，这些神经中去甲肾上腺素的过度释放应会导致胰高血糖素分泌增加，进而导致B细胞胰岛素分泌过度兴奋。这就是所谓“高胰岛素血症”中出现的紊乱，即血浆葡萄糖、胰岛素和胰高血糖素水平同时升高。考虑到神经交感活动与A5去甲肾上腺素能核和中缝正中5羟色胺能神经元呈正相关，与A6去甲肾上腺素能、背缝5羟色胺能和C1肾上腺素能神经元呈负相关，我们推测这种中枢神经系统回路失衡是高胰岛素血症综合征的原因。
