Defective regulation and action of atrial natriuretic peptide in type 2 diabetes.
Increased plasma atrial natriuretic peptide (ANP) levels and impaired ANP action have been reported in patients with diabetes or insulin resistance. The aim of this study was to assess the interaction between insulin and ANP in type 2 diabetes. In 12 normotensive, normoalbuminuric type 2 diabetics, we infused insulin at a high (6.6 pmol/min/kg) or, on a different day, at a low rate (0.6 pmol/min/kg) during 4 hours of isoglycemia under isovolumic, isoosmolar conditions. The normal response was established in 12 healthy volunteers using an identical protocol. Despite higher baseline ANP levels (17.7 +/- 2.8 vs. 10.8 +/- 1.8 pg/ml, p = 0.04), urinary sodium excretion was similar in diabetics and controls (113 +/- 8.5 vs. 102 +/- 8.8 mEq/24 hours, p = ns). In both groups, hyperinsulinemia caused a decrease in blood volume (0.33 +/- 0.10 l, p < 0.01), diastolic blood pressure (6 %, p < 0.02), and natriuresis. However, plasma ANP decreased in controls (from 12.7 +/- 1.9 to 8.6 +/- 1.4 pg/ml, p = 0.01) but not in type 2 diabetics (15.1 +/- 2.7 vs. 17.2 +/- 3.8 pg/ml, p = ns). We conclude that ANP release is resistant to volume stimulation in type 2 diabetic patients, and natriuresis is resistant to ANP action. This dual disruption of ANP control may play a role in blood pressure regulation in diabetes.
Nannipieri
M
M
Metabolism Unit of the C. N. R. Institute of Clinical Physiology, University of Pisa School of Medicine, Via Savi 8, 56100 Pisa, Italy.
Seghieri
G
G
Catalano
C
C
Prontera
T
T
Baldi
S
S
Ferrannini
E
E
D000328:Adult; D000368:Aged; D000450:Aldosterone / Q000097:blood; D009320:Atrial Natriuretic Factor / Q000097:blood / Q000502:physiology*; D001786:Blood Glucose / Q000378:metabolism; D001810:Blood Volume / Q000502:physiology; D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000503:physiopathology*; D004573:Electrolytes / Q000378:metabolism; D005260:Female; D015309:Glucose Clamp Technique; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D006946:Hyperinsulinism / Q000503:physiopathology; D007328:Insulin / Q000097:blood; D008297:Male; D008875:Middle Aged; D009318:Natriuresis / Q000502:physiology; D012083:Renin / Q000097:blood
D000450:Aldosterone; D009320:Atrial Natriuretic Factor; D001786:Blood Glucose; D004573:Electrolytes; D006442:Glycated Hemoglobin; D007328:Insulin; D012083:Renin