The effect of acute (60 minute) insulin stimulation upon human skeletal muscle glycogen synthase and protein phosphatase-1 in non-insulin-dependent diabetic patients and control subjects
| Autor: | S. J. Yeaman, A.M. Wells, S. J. Hurel, L. A. Barriocanal, M. Stewart, A. C. Borthwick, Robert W. Taylor |
|---|---|
| Rok vydání: | 1995 |
| Předmět: |
Blood Glucose
Male medicine.medical_specialty Time Factors Endocrinology Diabetes and Metabolism medicine.medical_treatment Biopsy Stimulation Fatty Acids Nonesterified Body Mass Index Gastrocnemius muscle Endocrinology Reference Values Internal medicine Diabetes mellitus Protein Phosphatase 1 Internal Medicine medicine Phosphoprotein Phosphatases Humans Insulin Glycogen synthase Infusions Intravenous Muscle Skeletal Triglycerides Glycated Hemoglobin biology business.industry Skeletal muscle Protein phosphatase 1 Middle Aged medicine.disease Enzyme Activation Kinetics medicine.anatomical_structure Glycogen Synthase Basal (medicine) Diabetes Mellitus Type 2 biology.protein Female business |
| Zdroj: | Diabetic medicine : a journal of the British Diabetic Association. 12(12) |
| ISSN: | 0742-3071 |
| Popis: | Previous studies have established that activation of muscle glycogen synthase (GS) is abnormal in non-insulin-dependent diabetes mellitus (NIDDM). Insulin-mediated activation of GS depends upon protein phosphatase-1 (PP1), which dephosphorylates the relevant sites of GS. In order to determine whether defects in PP1 activation cause subnormal activation of GS or whether PP1 activation itself is normal, we administered a short insulin infusion to 8 NIDDM subjects and 8 healthy controls matched for gender, age, and body mass index (BMI). GS fractional activity and PP1 activity were determined in biopsies taken from the gastrocnemius muscle before and after 60 min insulin infusion (0.1 U kg h-1). In the NIDDM group, muscle GS fractional activity was 6.8 +/- 1.6 and 10.0 +/- 1.5% (mean +/- SEM) (p = 0.11) before and after insulin infusion. In the control group, muscle GS fractional activity increased from 7.3 +/- 2.0 to 13.3 +/- 2.7% (p < 0.02). PP1 activity had returned towards basal levels after insulin infusion; NIDDM group 156 +/- 24.7 to 184.1 +/- 28.1 U mg-1; control group 220.8 +/- 30.1 to 233.8 +/- 29.8 U mg-1. In the NIDDM group there was a positive correlation between the increases in GS fractional activity and PP1 activity following insulin stimulation r = 0.77; p < 0.025). These data indicate that in vivo insulin-dependent activation of muscle PP1 is transient in normal subjects but is delayed in NIDDM. The defect in GS activation in NIDDM is likely to be proximal to PP1 in the pathway of transmission of the insulin signal. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text