Pathophysiology of type 2 diabetes and the impact of altered metabolic interorgan crosstalk

Abstract

Diabetes is a complex and multifactorial disease that affects millions of people worldwide, reducing the quality of life significantly, and results in grave consequences for our health care system. In type 2 diabetes (T2D), the lack of β‐cell compensatory mechanisms overcoming peripherally developed insulin resistance is a paramount factor leading to disturbed blood glucose levels and lipid metabolism. Impaired β‐cell functions and insulin resistance have been studied extensively resulting in a good understanding of these pathways but much less is known about interorgan crosstalk, which we define as signaling between tissues by secreted factors. Besides hormones and organokines, dysregulated blood glucose and long‐lasting hyperglycemia in T2D is associated with changes in metabolism with metabolites from different tissues contributing to the development of this disease. Recent data suggest that metabolites, such as lipids including free fatty acids and amino acids, play important roles in the interorgan crosstalk during the development of T2D. In general, metabolic remodeling affects physiological homeostasis and impacts the development of T2D. Hence, we highlight the importance of metabolic interorgan crosstalk in this review to gain enhanced knowledge of the pathophysiology of T2D, which may lead to new therapeutic approaches to treat this disease.

Risk of diaphragmatic hernia in patients with spontaneous pneumothorax

“…(Table 3). A previous study showed that smoking, older age, diabetes mellitus and hypertension can increase systemic soft tissue remodeling [20][21][22]. Therefore, our findings can be explained by the fact that the systemic predisposition of SP was strengthened by the abovementioned risk factors.…”

MMPP promotes adipogenesis and glucose uptake via binding to the PPARγ ligand binding domain in 3T3-L1 MBX cells

“…The body's system maintains glucose levels through the pair of opposing hormones, insulin and glucagon (Unger and Orci, 2010). However, type 2 diabetics have low insulin sensitivity, impaired glucose tolerance, and decreased insulin- Frontiers in Pharmacology frontiersin.org stimulated glucose uptake; therefore, glucose level becomes too high (Lebovitz, 2001;Sanches et al, 2021). PPARγ is a key regulator of adipogenic differentiation, and its role has been well established.…”

Type 2 Diabetes and the Microbiome

“…A full analysis of T2D pathophysiology is beyond the scope of this review, but, as discussed in a recent review by Galicia-Garcia et al [ 6 ], the mechanisms underlying insulin production and release, and its detection and uptake by target tissues, are all tightly regulated, and defects in any of these may lead to metabolic imbalances and ultimately to the development of T2D [ 3 , 6 ]. For example, impairments in any of the pathways involved in insulin binding can lead to reduced glucose uptake, resulting in higher circulating glucose levels (hyperglycemia) and placing increasing demands on insulin-producing pancreatic beta cells [ 3 , 7 ] and, as noted above, impaired insulin detection and/or uptake by target tissues such as skeletal muscle, adipose tissue, and the liver can result in insulin resistance [ 3 , 7 ]. Of note, this also leads to inflammation in the target tissues, with increases in circulating levels of proinflammatory cytokines [ 3 , 7 ].…”

“…For example, impairments in any of the pathways involved in insulin binding can lead to reduced glucose uptake, resulting in higher circulating glucose levels (hyperglycemia) and placing increasing demands on insulin-producing pancreatic beta cells [ 3 , 7 ] and, as noted above, impaired insulin detection and/or uptake by target tissues such as skeletal muscle, adipose tissue, and the liver can result in insulin resistance [ 3 , 7 ]. Of note, this also leads to inflammation in the target tissues, with increases in circulating levels of proinflammatory cytokines [ 3 , 7 ].…”