The role of glucose in diabetic hypertension: effects on intracellular cation metabolism.
The clinical association of hypertension, obesity, noninsulin-dependent diabetes mellitus (NIDDM), and other cardiovascular risk factors has long been recognized. The recent finding that essential hypertension is also an insulin-resistant state associated with hyperinsulinemia led some authors to attribute a role in mediating this association and in the pathogenesis of hypertension itself to insulin. However, evidence also exists independently of insulin per se that alterations in glucose metabolism in general, and of hyperglycemia in particular, may also contribute to the hypertensive process, especially in the hypertension of diabetes. The authors attempted to understand the relationship between glucose and insulin metabolism, diabetes, and hypertension from a cellular ionic point of view. In vitro it was shown that glucose, in a specific, dose- and time-dependent manner, can directly and coordinately alter intracellular ions, increasing cytosolic free calcium, while suppressing intracellular free magnesium and pH levels. These glucose-induced changes exactly parallel those ionic lesions previously observed in vivo in the fasting hyperglycemia of hypertension associated with NIDDM. These and other data led to the hypothesis that circulating blood glucose, independently of insulin and even at normal levels, is a physiologic determinant of cellular ion homeostasis. Furthermore, the cellular ionic consequences of hyperglycemia may contribute to the increased risk of hypertension and vascular diseases present among subjects with NIDDM, impaired glucose tolerance, or both.
Barbagallo
M
M
Cardiovascular Center, New York Hospital-Cornell Medical Center, New York.
Resnick
L M
LM
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D005947:Glucose / Q000502:physiology*; D006801:Humans; D006973:Hypertension / Q000209:etiology*; D008274:Magnesium / Q000378:metabolism*
D008274:Magnesium; D005947:Glucose; D002118:Calcium