Touchstone Center for Diabetes Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Endocr Pract. 2011 Sep-Oct;17(5):819-25. doi: 10.4158/EP11101.OR.
To determine whether glucagon suppression by leptin represents a direct effect on α cells rather than an indirect effect mediated via the hypothalamus.
We devised an in vitro α-cell suppression assay in cultured hamster InR1G9 cells. InR1G9 hamster cells were infected with adenovirus containing mouse leptin receptors, and they were then incubated with leptin, insulin, or somatostatin in concentrations known to suppress glucagon in vivo.
Whereas somatostatin and insulin both suppressed the increase in glucagon secretion stimulated by high levels of glucose, leptin had no such effect. This inability of leptin to suppress glucagon in vitro could signify that it acts indirectly by causing the release of glucagon-suppressing peptides from the hypothalamus or stomach. To search for such a peptide, we studied the effects on glucagon secretion of 6 neuropeptides: orexin, melanocyte-stimulating hormone, neuropeptide Y, cocaine and amphetamine regulated transcript, neurotensin, and Agouti-related peptide that might be involved in the hypothalamic action of leptin. None of these peptides suppressed glucagon at low, normal, or elevated glucose concentrations.
If the cultured α cells used faithfully mimic the leptin response of in situ α cells of the diabetic animal, the glucagon-suppressing action of leptin is indirect, but is not mediated by any 1 of the 6 neuropeptides tested.
确定瘦素对α细胞的抑制作用是否代表对α细胞的直接作用，而不是通过下丘脑介导的间接作用。
我们设计了一种在体外培养的仓鼠 InR1G9 细胞中抑制α细胞的测定方法。用携带小鼠瘦素受体的腺病毒感染 InR1G9 仓鼠细胞，然后用已知在体内抑制胰高血糖素的浓度的瘦素、胰岛素或生长抑素孵育。
虽然生长抑素和胰岛素都抑制了高葡萄糖刺激的胰高血糖素分泌的增加，但瘦素没有这种作用。瘦素在体外不能抑制胰高血糖素，这可能表明它通过从下丘脑或胃中释放抑制胰高血糖素的肽而间接起作用。为了寻找这种肽，我们研究了 6 种神经肽对胰高血糖素分泌的影响：食欲素、促黑素细胞激素、神经肽 Y、可卡因和安非他命调节转录物、神经降压素和 Agouti 相关肽，它们可能参与瘦素的下丘脑作用。这些肽在低、正常或升高的葡萄糖浓度下均不抑制胰高血糖素。
如果所使用的体外培养的α细胞忠实地模拟糖尿病动物体内α细胞对瘦素的反应，那么瘦素抑制胰高血糖素的作用是间接的，但不是由我们测试的 6 种神经肽中的任何一种介导的。
