Lack of glucose uptake compromises metabolic flexibility and reduces energy efficiency in the diabetes mellitus (DM) heart. Although increased utilization of fatty acid to compensate glucose substrate has been studied, less is known about ketone body metabolism in the DM heart. Ketogenic diet reduces obesity, a risk factor for T2DM. How ketogenic diet affects ketone metabolism in the DM heart remains unclear. At the metabolic level, the DM heart differs from the non-DM heart due to altered metabolic substrate and the T1DM heart differs from the T2DM heart due to insulin levels. How these changes affect ketone body metabolism in the DM heart are poorly understood. Ketogenesis produces ketone bodies by utilizing acetyl CoA whereas ketolysis consumes ketone bodies to produce acetyl CoA, showing their opposite roles in the ketone body metabolism. Cardiac-specific transgenic upregulation of ketogenesis enzyme or knockout of ketolysis enzyme causes metabolic abnormalities leading to cardiac dysfunction. Empirical evidence demonstrates upregulated transcription of ketogenesis enzymes, no change in the levels of ketone body transporters, very high levels of ketone bodies, and reduced expression and activity of ketolysis enzymes in the T1DM heart. Based on these observations, I hypothesize that increased transcription and activity of cardiac ketogenesis enzyme suppresses ketolysis enzymes in the DM heart, which decreases cardiac energy efficiency. The T1DM heart exhibits highly upregulated ketogenesis compared to T2DM due to lack of insulin that inhibits ketogenesis enzyme.

中文翻译：

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为什么糖尿病心脏能量效率低下：生酮和酮解的观点

葡萄糖摄取不足会损害代谢灵活性并降低糖尿病 (DM) 心脏的能量效率。尽管已经研究了增加利用脂肪酸来补偿葡萄糖底物，但对 DM 心脏中的酮体代谢知之甚少。生酮饮食可减少肥胖，这是 T2DM 的危险因素。生酮饮食如何影响 DM 心脏中的酮代谢尚不清楚。在代谢水平上，DM 心脏因代谢底物改变而与非 DM 心脏不同，T1DM 心脏因胰岛素水平而与 T2DM 心脏不同。这些变化如何影响 DM 心脏中的酮体代谢尚不清楚。生酮通过利用乙酰辅酶A产生酮体，而酮解消耗酮体产生乙酰辅酶A，显示它们在酮体代谢中的相反作用。生酮酶的心脏特异性转基因上调或酮解酶的敲除会导致代谢异常，导致心脏功能障碍。经验证据表明，T1DM 心脏中生酮酶的转录上调，酮体转运蛋白水平没有变化，酮体水平非常高，以及酮解酶的表达和活性降低。基于这些观察，我假设心脏生酮酶的转录和活性增加会抑制 DM 心脏中的酮解酶，从而降低心脏能量效率。由于缺乏抑制生酮酶的胰岛素，T1DM 心脏与 T2DM 相比表现出高度上调的生酮。