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Effects of Intensive Dietary Treatment on Insulin‐stimulated Skeletal Muscle Glycogen Synthase Activation and Insulin Secretion in Newly Presenting Type 2 Diabetic Patients
Author(s) -
Johnson A.B.,
Argyraki M.,
Thow J.C.,
Broughton D.,
Jones I.R.,
Taylor R.
Publication year - 1990
Publication title -
diabetic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.474
H-Index - 145
eISSN - 1464-5491
pISSN - 0742-3071
DOI - 10.1111/j.1464-5491.1990.tb01417.x
Subject(s) - medicine , endocrinology , nefa , insulin , glycogen synthase , glycogen , diabetes mellitus , skeletal muscle , type 2 diabetes
Ten newly presenting, untreated, Europid Type 2 diabetic patients were studied before and after 8 weeks treatment with intensive diet alone. Nine normal control subjects were also studied. The degree of activation of skeletal muscle glycogen synthase (GS) was used as an intracellular marker of insulin action, prior to and during a 240‐min insulin infusion (100 mU kg −1 h −1 ). Fasting blood glucose decreased from 12.1 ± 0.9 (±SE) to 9.2 ± 0.8 mmol I −1 ( p < 0.01), but there was no change in fasting insulin concentrations, 9.9 ± 2.3 vs 9.3 ± 2.1 mU I −1 . Fractional GS activity did not increase in the Type 2 diabetic patients during the insulin infusion either at presentation (change −1.5 ± 1.9%) or after treatment (change +0.9 ± 1.8%), and was markedly decreased compared with the control subjects (change +14.5 ± 2.8%, both p < 0.001). Glucose requirement during the clamp was decreased in the Type 2 diabetic patients at presentation (2.2 ± 0.7 vs 7.3 ± 0.6 mg kg −1 min −1 , p < 0.001), and despite improvement following dietary treatment to 3.3 ± 0.6 mg kg −1 min −1 ( p < 0.01) remained lower than in the control subjects ( p < 0.001). Fasting plasma non‐esterified fatty acid (NEFA) concentrations were elevated at presentation ( p < 0.05), and failed to suppress normally during the insulin infusion. After treatment fasting NEFA concentrations decreased ( p < 0.05) and suppressed normally ( p < 0.05). Insulin secretion was assessed following an intravenous bolus of glucose (0.5 g kg −1 ) at euglycaemia before and after treatment. Both first (1 ± 1 vs 53 ± 9 mU I −1 , p < 0.001) and second (148 ± 129 vs 781 ± 207 mU I −1 min, p < 0.02) phase responses were decreased compared with the control subjects. Following treatment the first phase response remained abnormal (2 ± 3 mU I −1 ), while the second phase response improved markedly (459 ± 206 mU I −1 min, p < 0.05), and was no longer significantly different to the control group. Thus the improved blood glucose control in the diet‐treated newly presenting Type 2 diabetic patients is likely to result from both increased insulin secretion and increased insulin action. The inability of insulin to activate skeletal muscle GS after treatment is likely to underlie the continued insulin insensitivity in these patients.