Effect of glucose, insulin, and hypertonicity on atrial natriuretic peptide levels in man

Abstract

To determine the effect of hyperglycemia and hyperinsulinemia on atrial natriuretic peptide (ANP) levels in man, we studied normotensive nondiabetic volunteers (aged 25 to 63 years) during infusion of insulin and/or 20% dextrose (glucose clamp technique) to achieve three different states of “glycemia/hyperinsulinemia,” as follows: (1) euglycemia for 2 hours during infusion of insulin (80 mU · m −2 · min −1), resulting in plasma insulin levels of approximately 1,200 pmol/L (n = 9); (2) moderate stable hyperglycemia at a level of 11 mmol/L (198 mg/dL) for 2 hours, with infusion of glucagon-like peptide-1 (7–37) amide (GLP-1) during the second hour, which increased endogenous insulin responses to approximately 2,100 pmol/L (n = 9); and (3) marked stable hyperglycemia at a level of 18.5 mmol/L (330 mg/dL) for 2 hours, with endogenous insulin responses of approximately 720 pmol/L (n = 9). In addition, six patients with non-insulin-dependent diabetes mellitus were studied with the GLP-1 protocol at a hyperglycemic level of 14.5 mmol/L (261 mg/dL). In normal subjects, plasma ANP levels increased significantly from 3.0 ± 0.4 to 4.6 ± 0.8 pmol/L during marked hyperglycemia, but did not change during euglycemia or moderate hyperglycemia despite higher insulin levels ( P < .01, ANOVA). Sodium excretion rates were also highest during the marked hyperglycemic study (125 ± 14 v 91 ± 7 v 74 ± 10 μmol/min, P < .05, marked v moderate hyperglycemia v euglycemia). In diabetic subjects, ANP levels increased significantly from 12.5 ± 4.1 to 21.1 ± 5.0 pmol/L during hyperglycemia. To determine the contribution of hypertonicity to the increases in ANP levels, seven subjects underwent infusion of 5% saline and 0.9% saline on separate occasions to produce equivalent degrees of volume expansion. Hypertonicity was shown to contribute significantly to ANP elevation, as the increment in ANP levels was significantly greater with 5% saline than with 0.9% saline despite similar changes in plasma volume. In summary, marked hyperglycemia produced acutely can increase plasma ANP levels via a mechanism that is unrelated to hyperinsulinemia; the mechanism may be related to an increase in both plasma tonicity and volume. Hyperglycemia may contribute to the increased circulating ANP levels observed in diabetic subjects.