Effect of Acidosis on Insulin Binding and Glucose Uptake in Isolated Rat Adipocytes.

Abstract

A., TOMINAGA, M. and SASAKI, H. Effect of Acidosis on Insulin Binding and Glucose Uptake in Isolated Rat Adipocytes. Tohoku J. Exp. Med., 1993, 169 (3), 205-213 To assess the mechanism of insulin resistance in metabolic acidosis, we investigated insulin receptor binding and glucose uptake in isolated rat epididymal adipocytes at three pHs, acidic (pH 6.8), neutral (pH 7.4) and alkaline (pH 8.0) groups. After male Sprague-Dawley rats weighing 220-240 g were submitted under chloral hydrate anesthesia, epididymal fat pads were dissected and isolated. [12511-insulin binding rate was not different between alkaline and neutral groups, but that of acidic group was markedly decreased to approximately 30% of neutral group at maximum specific insulin binding rate. Scatchard analysis showed that numbers of insulin receptors were not different among three groups, but values of binding affinity in acidic group was significantly lower than those of the others. 2-[3H]deoxy-D-glucose uptake of alkaline and neutral groups were increased to reach steady state immediately, but that of acidic group increased slowly and reached at maximum which was lower than the other two groups. Furthermore, 2-deoxy-D-glucose uptake against amount of bound insulin was lower in acidic group than other two groups. From these results, it is suggested that insulin resistance in metabolic acidosis resulted from the combined defects in binding affinity and post-binding process in the insulin receptor. insulin resistance ; acidosis ; insulin receptor ; glucose uptake ; adipocyte

Mechanisms of Metabolic Acidosis–Induced Kidney Injury in Chronic Kidney Disease

“…17 The defect in insulin sensitivity associated with metabolic acidosis results from alteration in downstream signaling and not an alteration in insulin receptor binding. 175,176 A recent study evaluated whether metabolic acidosis treated with NaHCO 3 reduced insulin use in people with type 2 diabetes and CKD. 177 The investigators prospectively explored the association of serum bicarbonate as a continuous variable and insulin resistance over a broad range of values of serum bicarbonate (i.e., from 18 to 31 mEq/L).…”

Plasma bicarbonate and risk of type 2 diabetes mellitus

“…Diet exposures and physical activity were calculated as updated cumulative average levels as of the baseline (1990) questionnaire. We also summarized intake of cereal fibre and trans fats, glycemic load and the ratio of polyunsaturated to saturated fats (with each component categorized in quintiles and scored 1-5, where 5 was assigned to the healthiest intake) in a diabetes diet score (ranging from [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20], with a high diet score associated with a reduced risk of type 2 diabetes mellitus in the Nurses' Health Study. 16 The reproducibility and validity of the food-frequency questionnaires have been described.…”

Consequences and therapy of the metabolic acidosis of chronic kidney disease

“…Studies in rats showed that metabolic acidosis was associated with impaired glucose tolerance and insulin resistance [87–90]. In vitro experiments revealed that the insulin resistance was attributed, in part, to pH-related impaired binding of insulin to its receptors [89, 90].…”

“…In vitro experiments revealed that the insulin resistance was attributed, in part, to pH-related impaired binding of insulin to its receptors [89, 90]. Experiments in humans with normal renal function using both the euglycemic and hyperglycemic clamp technique revealed that ammonium chloride-induced metabolic acidosis resulted in reduced tissue sensitivity to insulin [91].…”