Sener A, Kadiata M M, Olivares E, Malaisse W J
Laboratory of Experimental Medicine, Brussels Free University, Belgium.
Diabetologia. 1998 Sep;41(9):1109-13. doi: 10.1007/s001250051037.
It was recently, and surprisingly, found that D-mannoheptulose did not affect D-glucose metabolism and insulinotropic action in pancreatic islets incubated at a low concentration of D-glucose. To explain this finding, the metabolism and secretory response to the hexose were investigated in rat islets exposed to D-mannoheptulose hexaacetate, which was recently found to inhibit D-glucose catabolism in cells that are otherwise fully resistant to the heptose. At a high concentration of D-glucose (16.7 mmol/l), the utilisation of D-[5-(3)H]glucose and oxidation of D-[U-14C]glucose, as well as the insulinotropic action of the hexose, were affected less by D-mannoheptulose tetraacetate than by unesterified D-mannoheptulose. This coincided with a reduced uptake of the ester by intact islets and a lower rate of hydrolysis of the ester in islet homogenates compared with findings in other monosaccharide esters such as D-glucose pentaacetate. At a low concentration of D-glucose (2.8 mmol/l), D-mannoheptulose hexaacetate was slightly more efficient than the unesterified heptose in reducing D-glucose catabolism, but still failed to suppress the secretory response to the hexose. These findings do not necessarily mean that unesterified D-mannoheptulose enters beta-cells more efficiently at high than at low extracellular D-glucose concentrations, especially if possible differences in the respective contributions of distinct islet cell types to the overall catabolism of D-glucose by whole islets is allowed for. These data do not rule out the possibility that D-glucose phosphorylation is more resistant to D-mannoheptulose in beta cells incubated at a low than a high concentration, independently of any difference in the intracellular concentration of the heptose. However, the mechanism of this resistance is still not explained.
最近令人惊讶地发现，在低浓度D - 葡萄糖孵育的胰岛中，D - 甘露庚酮糖不影响D - 葡萄糖代谢和促胰岛素作用。为了解释这一发现，研究了暴露于D - 甘露庚酮糖六乙酸酯的大鼠胰岛对己糖的代谢和分泌反应，最近发现该物质可抑制原本对庚糖完全耐药的细胞中的D - 葡萄糖分解代谢。在高浓度D - 葡萄糖（16.7 mmol/L）时，D - [5 - (3)H]葡萄糖的利用和D - [U - 14C]葡萄糖的氧化以及己糖的促胰岛素作用，受D - 甘露庚酮糖四乙酸酯的影响小于未酯化的D - 甘露庚酮糖。这与完整胰岛对该酯的摄取减少以及胰岛匀浆中该酯的水解速率低于其他单糖酯（如D - 葡萄糖五乙酸酯）的情况一致。在低浓度D - 葡萄糖（2.8 mmol/L）时，D - 甘露庚酮糖六乙酸酯在降低D - 葡萄糖分解代谢方面比未酯化的庚糖略有效，但仍未能抑制对己糖的分泌反应。这些发现不一定意味着在细胞外D - 葡萄糖浓度高时未酯化的D - 甘露庚酮糖比低时更有效地进入β细胞，特别是如果考虑到不同胰岛细胞类型对整个胰岛D - 葡萄糖总体分解代谢的各自贡献可能存在差异。这些数据不排除在低浓度而非高浓度孵育的β细胞中，D - 葡萄糖磷酸化对D - 甘露庚酮糖更具抗性的可能性，而与庚糖细胞内浓度的任何差异无关。然而，这种抗性的机制仍未得到解释。
