Cytosolic Calcium and Insulin Resistance in Elderly Patients With Essential Hypertension

Abstract

We evaluated insulin sensitivity in normotensive (blood pressure, BP, less than 135/85 mm Hg) and hypertensive (BP greater than 160/90 mm Hg) elderly subjects over 65 years old who were stratified as normal weight (body mass index, BMI, less than 27) and obese (BMI greater than 27). Obese hypertensive individuals demonstrated marked hyperinsulinemia (P less than .01) and significantly reduced (P less than .05) submaximally stimulated adipocyte 2-deoxyglucose (2-DOG) uptake (abdominal wall fat biopsy). Normal weight hypertensive subjects also demonstrated higher levels of insulinemia and lower insulin-stimulated 2-DOG uptake than nonobese controls. Adipocyte [Ca2+]i levels were elevated in all elderly subjects compared to young individuals (P less than .01). Basal and maximally stimulated 2-DOG uptake were similar in all groups. One month of therapy with a calcium channel blocker, 10 mg nitrendipine twice daily, reduced blood pressure in the hypertensive subjects, reduced plasma insulin to control values during an oral glucose tolerance test in obese hypertensive individuals (P less than .01), and restored adipocyte 2-DOG uptake at submaximally effective insulin concentration to control values in normal weight and obese hypertensive subjects. In summary, older hypertensive, and particularly older obese hypertensive, patients manifest significant insulin resistance accompanied by elevated levels of [Ca2+]i in their adipocytes.

Serum calcium is independently associated with insulin sensitivity measured with euglycaemic–hyperinsulinaemic clamp in a community-based cohort

“…This is supported by previous experimental data [8,9]. Increasing intracellular calcium levels have been shown to decrease the effect of insulin in adipocytes due to the reduced number of glucose transporters (GLUT4) and decreased insulin receptor activity [4,[28][29][30][31]. In an autopsy study performed in consecutive patients, it was shown that parathyroid adenomas and hyperplasia were far more common than the expected prevalence of overt hypercalcaemia [32].…”

Agouti regulation of intracellular calcium: role in the insulin resistance of viable yellow mice.

“…In addition, Ca2+ entry blockade in obese elderly humans resulted in significant increases in peripheral insulin sensitivity (15,16 phosphorylation of Glut4 appeared to be mediated by Ca2+-induced phosphorylation and activation of inhibitor 1, which functions to inhibit phosphoserine phosphatase 1 activity (18). Overall, based on these findings, we predict that the hyperinsulinemia/insulin resistance in the yellow obese mutants causes increased [Ca2+]i in soleus muscle, which induces increased activity of inhibitor 1.…”

Effects of Aging on Serum Ionized and Cytosolic Free Calcium

“…1,2 In the steady state, altered calcium and magnesium levels are present in essential hypertension and in non-insulindependent diabetes mellitus (NIDDM). 2 Elevated basal cytosolic free calcium (Ca i ) levels, as well as defective membrane binding and transport kinetics of calcium, have been identified in platelets, 3 erythrocytes, 4 lymphocytes, 5 and adipocytes 6 of hypertensive subjects, in whom blood pressure levels were closely and directly related to Ca i content. 3,4 In diabetes, even in the absence of overt hypertension, Ca i levels were similarly elevated, 4 and defective calcium handling has been found in all diabetic tissues tested thus far, including cardiac and skeletal muscle, arteries, kidney, liver, erythrocytes, osteoblasts, adipocytes, and platelets.…”