Recent Advances in the Treatment of Insulin Resistance Targeting Molecular and Metabolic Pathways: Fighting a Losing Battle?

Abstract

Diabetes Mellitus (DM) is amongst the most notable causes of years of life lost worldwide and its prevalence increases perpetually. The disease is characterized as multisystemic dysfunctions attributed to hyperglycemia resulting directly from insulin resistance (IR), inadequate insulin secretion, or enormous glucagon secretion. Insulin is a highly anabolic peptide hormone that regulates blood glucose levels by hastening cellular glucose uptake as well as controlling carbohydrate, protein, and lipid metabolism. In the course of Type 2 Diabetes Mellitus (T2DM), which accounts for nearly 90% of all cases of diabetes, the insulin response is inadequate, and this condition is defined as Insulin Resistance. IR sequela include, but are not limited to, hyperglycemia, cardiovascular system impairment, chronic inflammation, disbalance in oxidative stress status, and metabolic syndrome occurrence. Despite the substantial progress in understanding the molecular and metabolic pathways accounting for injurious effects of IR towards multiple body organs, IR still is recognized as a ferocious enigma. The number of widely available therapeutic approaches is growing, however, the demand for precise, safe, and effective therapy is also increasing. A literature search was carried out using the MEDLINE/PubMed, Google Scholar, SCOPUS and Clinical Trials Registry databases with a combination of keywords and MeSH terms, and papers published from February 2021 to March 2022 were selected as recently published papers. This review paper aims to provide critical, concise, but comprehensive insights into the advances in the treatment of IR that were achieved in the last months.

Keywords: glucose metabolism; insulin resistance; metabolic syndrome; obesity; type 2 diabetes.

Figure 1

Overview of insights into the most common causes and main outcomes of IR. Insulin resistance is caused by a plethora of metabolic changes in lipid, glucose and hormone status as well as chronic oxidative stress and a chronic inflammatory state [2,3]. The main outcomes include, but are not limited to, increased risk of CVD, alterations in lipid and glucose metabolism, and lower life quality in general [4,5].

Figure 2

PRISMA-based scheme describing the search strategy.

Figure 3

Schematic graph showing the effects of various agents on AMPK signalling with their subsequent impacts. Recently, many different agents targeting the AMPK-related pathways have been proposed as a novel approach for IR treatment. Using them leads to improved glucose and lipid metabolism and attenuates inflammation and oxidative stress parameters, as well as stimulating molecular pathways that are protective against IR progression [52,53,54,55,56,57,58,59].