Summary
Hepatic glucose production and metabolic clearance rate of glucose were measured using (3-3H) glucose at steady state, basally and during two sequential 2 h insulin (25 and 40mU · kg–1 · h–1)/glucose(2 and 3mg · kg–1 · min–1) infusion periods. Eight diabetic subjects were studied before and after 1 week of twice daily insulin therapy; six control subjects matched for age, weight and degree of obesity were also studied. In the diabetic patients, pre-treatment hepatic glucose production was 20.0 ± 2.2, 9.9 ± 2.9, and 1.4 ± 0.8 μmol · kg–1 · min–1 respectively (± SEM) for each of the three periods, and fell significantly with treatment to 12.8 ± 1.7,4.0 ± 1.5 and 1.9 ± 1.0 μmol · kg–1 · min–1. Hepatic glucose production in normal subjects was 13.2 ± 0.6, 2.2 ± 0.8 and < 1 μmol · kg–1 · min–1. The pre-treatment metabolic clearance rate in all diabetic studies with insulin levels ⩾ 30 mU/l was 1.10 ± 0.14 ml · kg–1 · min–1 and remained virtually unchanged following insulin therapy; this was significantly lower than in the control subjects (6.83 ± 1.02, p < 0.001). Basal non-esterified fatty acid levels were higher (p < 0.02) in the pre-treated diabetic patients compared to post-treated diabetic patients and control subjects. Non-esterified fatty acids in each group fell to similar levels during the insulin infusions, but the rate of fall was slower in the pre-treated diabetic patients. Insulin receptor binding to erythrocytes was normal in the diabetic subjects and unchanged by treatment. Therefore, following insulin treatment of uncontrolled Type 2 (non-insulin-dependent) diabetes, the initially increased basal hepatic glucose production, and decreased hepatic sensitivity, return towards normal. However, the glucose clearance remains low, despite good diabetic control, and appears to be a major factor in the continuing glucose intolerance. As insulin receptor binding is normal, the defect of glucose clearance in Type 2 diabetes appears compatible with a post-receptor defect of glucose metabolism.
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Nankervis, A., Proietto, J., Aitken, P. et al. Differential effects of insulin therapy on hepatic and peripheral insulin sensitivity in Type 2 (non-insulin-dependent) diabetes. Diabetologia 23, 320–325 (1982). https://doi.org/10.1007/BF00253737
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DOI: https://doi.org/10.1007/BF00253737