Department of Physiology, University of Toronto, 1 King's College Circle, Toronto, ON, Canada.
Diabetes Obes Metab. 2011 Oct;13 Suppl 1:112-7. doi: 10.1111/j.1463-1326.2011.01451.x.
In type-2 diabetes, hyperglucagonaemia aggravates elevated blood glucose levels. Relative to our knowledge of the β-cell and insulin secretion, there remains a limited understanding of glucagon secretion in α-cells. Regulation of glucagon may be dependent on a combination of factors, which include direct glucose sensing by the α-cell, innervations from the autonomic nervous system and potential 'paracrine' actions by hormones and factors that are released by adjacent endocrine cells within the islets. The list of potential 'paracrine' regulators within the islet includes insulin, somatostatin, γ-aminobutyric acid, glutamate and zinc. Zinc crystallises with insulin in β-cells and is co-secreted with insulin. In the scientific literature, the effect of exogeneous zinc on glucagon secretion has been debated. Here, we confirm that an increase in exogeneous zinc does inhibit glucagon secretion. To determine if there are physiological effects of zinc on glucagon secretion we used a β-cell-specific ZnT8 knockout (Znt8BKO) mouse model. Znt8BKO mice, despite showing lower granular zinc content in β-cells, showed no changes in fasted plasma glucagon levels and glucose regulated glucagon secretion. These findings suggest that zinc secreted from β-cell does not regulate glucagon secretion.
在 2 型糖尿病中，高胰高血糖素血症加重了升高的血糖水平。相对于我们对β细胞和胰岛素分泌的了解，人们对α细胞中胰高血糖素的分泌知之甚少。胰高血糖素的调节可能依赖于多种因素，包括α细胞的直接葡萄糖感应、自主神经系统的神经支配以及激素和由胰岛内相邻内分泌细胞释放的潜在“旁分泌”作用。胰岛内潜在的“旁分泌”调节剂包括胰岛素、生长抑素、γ-氨基丁酸、谷氨酸和锌。锌与β细胞中的胰岛素结晶，并与胰岛素一起被分泌。在科学文献中，外源性锌对胰高血糖素分泌的影响一直存在争议。在这里，我们证实外源性锌的增加确实抑制了胰高血糖素的分泌。为了确定锌对胰高血糖素分泌是否有生理作用，我们使用了β细胞特异性 ZnT8 敲除（Znt8BKO）小鼠模型。尽管 Znt8BKO 小鼠β细胞中的颗粒状锌含量较低，但它们的空腹血浆胰高血糖素水平和葡萄糖调节的胰高血糖素分泌没有变化。这些发现表明，β细胞分泌的锌不调节胰高血糖素的分泌。
