Insulin Clearance in Obesity and Type 2 Diabetes

Abstract

Plasma insulin clearance is an important determinant of plasma insulin concentration. In this review, we provide an overview of the factors that regulate insulin removal from plasma and discuss the interrelationships among plasma insulin clearance, excess adiposity, insulin sensitivity, and type 2 diabetes (T2D). We conclude with the perspective that the commonly observed lower insulin clearance rate in people with obesity, compared with lean people, is not a compensatory response to insulin resistance but occurs because insulin sensitivity and insulin clearance are mechanistically, directly linked. Furthermore, insulin clearance decreases postprandially because of the marked increase in insulin delivery to tissues that clear insulin. The commonly observed high postprandial insulin clearance in people with obesity and T2D likely results from the relatively low insulin secretion rate, not an impaired adaptation of tissues that clear insulin.

Standardized Ethanol Extract of Cassia mimosoides var. nomame Makino Ameliorates Obesity via Regulation of Adipogenesis and Lipogenesis in 3T3-L1 Cells and High-Fat Diet-Induced Obese Mice

“…Insulin is a hormone secreted by pancreatic β cells, and the regulation of insulin clearance in the plasma is weak in obese subjects and patients with T2D [ 23 ]. Insulin concentration in the plasma of overweight individuals has been shown to correlate with plasma leptin levels [ 24 ].…”

Melatonin increases susceptibility to atrial fibrillation in obesity via Akt signaling impairment in response to lipid overload

“…29,30,47 In addition, fasting insulin levels are affected by both β-cell secretion and hepatic clearance of insulin. 48 It has been reported that obese and Type 2 diabetes patients commonly have a lower insulin clearance rate, 49 probably as a compensatory response to impaired β-cell function. In this study, we observed low C-peptide levels and a high insulin/C-peptide ratio in MLT-treated obese mice, which might also be a compensatory response to impaired β-cell function; therefore, MLT treatment impaired insulin secretion response but did not affect FINs levels in obese mice (Supporting Information: Figure 4).…”

Regulation of Insulin Clearance by Non-Esterified Fatty Acids

“…Nonetheless, reduced insulin clearance predictably limits the dependence on the compensatory increase in insulin secretion in order to spare the functionality of β-cells [ 36 ]. On the other hand, insulin clearance, especially post-prandial, has been shown to be higher in subjects with type 2 diabetes than those without the disease [ 37 ]. This appears to be related to defective insulin secretion and its resultant postprandial insulin delivery rate to its clearance sites.…”