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

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.

Triglyceride-glucose index, symptomatic intracranial artery stenosis and recurrence risk in minor stroke patients with hypertension

“…IR contributes to the development of lipid disorders [ 27 ] and accelerates the production of connective tissue in the vessel wall and the aggregation of LDL-C into the arterial smooth muscle [ 28 ]. Additionally, overproduction of insulin increases the inflammatory response at the endothelium and reduces the synthesis and utilization of nitric oxide in endothelial cells, affecting the normal function of the endothelium [ 29 ]. IR produces more reactive oxygen species and induces an abnormal increase in cytokines and inflammatory factors, leading to lipid peroxidation and endothelial damage and ultimately promoting the formation of atherosclerosis [ 30 ].…”

Efek Sitokin Proinflamasi TnF - Alpha pada Penyakit Diabetes Melitus Tipe 2: Tinjauan Literatur

“…8 Resistensi insulin merupakan keadaan yang mendasari terjadinya diabetes melitus tipe 2 yang merupakan suatu keadaan yang bersifat patologi dengan ditandai adanya hiperglikemia yang disebabkan oleh fungsi insulin terganggu berkaitan dengan sekresi insulin maupun fungsi. 9,10 Sementara etiologi semua jenis diabetes bervariasi, diet seimbang, sebagai salah satu faktor risiko reversibel memainkan peran utama dalam tiaptiap jenisnya dalam mencapai dan mempertahankan kontrol metabolisme yang baik, yang bersama dengan modifikasi gaya hidup yang sedang berlangsung. 11 Diabetes melitus tipe II (DMT2) adalah penyakit multifaktorial dan penyebab utama kematian dini.…”

Molecular Mechanisms for the Vicious Cycle between Insulin Resistance and the Inflammatory Response in Obesity

“…Moreover, the molecular mechanisms for IR also include insulin receptor antibodies, gene polymorphisms, and negative regulation of IRSs, as well as negative regulation of PI3K/AKT/mTOR and MAPK/ERK signaling. All of the above mechanisms are extensively reviewed in the cited references [ 122 , 123 , 124 , 125 , 126 , 127 , 128 , 129 , 130 ].…”