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Review
. 2022 Sep 8;14(9):e28944.
doi: 10.7759/cureus.28944. eCollection 2022 Sep.

Insulin Resistance and Type 2 Diabetes Mellitus: An Ultimatum to Renal Physiology

Susmita Sinha  1 , Mainul Haque  2
Affiliations
Review

Insulin Resistance and Type 2 Diabetes Mellitus: An Ultimatum to Renal Physiology

Susmita Sinha et al. Cureus. .

Abstract

Insulin resistance (IR) is stated as diminished insulin action regardless of hyperinsulinemia. The usual target organs for insulin activities are the liver, skeletal muscle, and adipose tissue. Hence, the vasculature and kidneys are nonconventional target organs as the impacts of insulin on these are comparatively separate from other conventional target organs. Vasodilation is achieved by raising endothelial nitric oxide (NO) generation by initiating the phosphoinositide 3-kinase (PI3K) pathway. In insulin-nonresponsive conditions, this process is defective, and there is increased production of endothelin-1 through the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway, which predominates the NO effects, causing vasoconstriction. Renal tubular cells and podocytes have insulin receptors, and their purposeful importance has been studied, which discloses critical acts of insulin signaling in podocyte survivability and tubular action. Diabetic nephropathy (DN) is a prevalent problem in individuals with hypertension, poor glycemic management, hereditary susceptibility, or glomerular hyperfiltration. DN could be a significant contributing factor to end-stage renal disease (ESRD) that results from chronic kidney disease (CKD). IR and diabetes mellitus (DM) are the constituents of syndrome X and are accompanied by CKD progression. IR performs a key part in syndrome X leading to CKD. However, it is indistinct whether IR individually participates in enhancing the threat to CKD advancement rather than CKD complexity. CKD is an extensive public health problem affecting millions of individuals worldwide. The tremendous spread of kidney disease intensifies people's health impacts related to communicable and noncommunicable diseases. Chronic disease regulator policies do not include CKD at global, local, and/or general levels. Improved knowledge of the character of CKD-associated problems might aid in reforming diagnosis, prevention, and management.

Keywords: chronic kidney disease; diabetes mellitus; end-stage renal disease (esrd); insulin; insulin resistance; nitric oxide; pi3k pathway; podocytes; renal tubular cells; vasodilation.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Diagrammatic representation of the study method.
IR: insulin resistance; NO: nitric oxide; PI3K: phosphoinositide 3-kinase; CKD: chronic kidney disease Image credit: Susmita Sinha
Figure 2
Figure 2. Schematic drawing of a typical nephron, glomerulus, and glomerular filtration barrier.
Image credit: Susmita Sinha
Figure 3
Figure 3. Insulin signaling pathway in podocytes.
PTP1B: protein tyrosine phosphatase 1B; IRS: insulin receptor substrate; PI3K: phosphoinositide 3-kinase; PIP2: phosphatidylinositol 4,5-bisphosphate; PIP3: phosphatidylinositol 3,4,5-triphosphate; PTEN: phosphatase and tensin homolog; PDK1: phosphoinositide-dependent kinase-1; PKB/Akt: protein kinase B; GLUT-4: glucose transporter type 4 Image credit: Susmita Sinha
Figure 4
Figure 4. Schematic diagram showing the effects of diabetes on glucose transporters and glucose transport on podocytes.
GLUT: glucose transporter; IRS1: insulin receptor substrate-1; Akt: protein kinase B Image credit: Susmita Sinha
Figure 5
Figure 5. Process of the generation of renal injury in insulin resistance.
NO: nitric oxide Image credit: Susmita Sinha
See this image and copyright information in PMC

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