Implications of Hydrogen Sulfide in Glucose Regulation: How H₂S Can Alter Glucose Homeostasis through Metabolic Hormones

Abstract

Diabetes and its comorbidities continue to be a major health problem worldwide. Understanding the precise mechanisms that control glucose homeostasis and their dysregulation during diabetes are a major research focus. Hydrogen sulfide (H2S) has emerged as an important regulator of glucose homeostasis. This is achieved through its production and action in several metabolic and hormone producing organs including the pancreas, liver, and adipose. Of importance, H2S production and signaling in these tissues are altered during both type 1 and type 2 diabetes mellitus. This review first examines how H2S is produced both endogenously and by gastrointestinal microbes, with a particular focus on the altered production that occurs during obesity and diabetes. Next, the action of H2S on the metabolic organs with key roles in glucose homeostasis, with a particular focus on insulin, is described. Recent work has also suggested that the effects of H2S on glucose homeostasis goes beyond its role in insulin secretion. Several studies have demonstrated important roles for H2S in hepatic glucose output and adipose glucose uptake. The mechanism of H2S action on these metabolic organs is described. In the final part of this review, future directions examining the roles of H2S in other metabolic and glucoregulatory hormone secreting tissues are proposed.

Recombinant Sox Enzymes from <i>Paracoccus pantotrophus</i> Degrade Hydrogen Sulfide, a Major Component of Oral Malodor

“…The Sox system appears to be advantageous in this point because its target is H 2 S produced by oral bacteria, not oral bacteria or oral tissues. Furthermore, previous studies reported that H 2 S participates in physiological regulation in the human body (28, 46, 50). Therefore, the Sox system has potential as an effective agent for controlling body systems as a H 2 S regulator.…”

Hydrogen Sulfide Affects Radical Formation in the Hippocampus of LPS Treated Rats and the Effect of Antipsychotics on Hydrogen Sulfide Forming Enzymes in Human Cell Lines

“…Hayden et al ( 59 ) have also shown elevated blood glucose levels after exposure with H 2 S. Pichette and Gagnon summarize the literature on the effects of H 2 S and glucose regulation, indicating that mechanisms besides insulin regulation, such as glucagon-like-peptide (GLP)-1 or peptide YY are involved ( 60 ). Our data confirm findings of Lin et al ( 61 ) that exogenous H 2 S protects cells by its glucose reducing activity.…”

Uterine Dysfunction in Diabetic Mice: The Role of Hydrogen Sulfide

“…Diabetes mellitus (DM), either type-1 diabetes mellitus (T1DM) or type-2 diabetes mellitus (T2DM), is a lifelong condition that affects millions of individuals worldwide [ 1 , 2 ], and it represents a strong risk factor for the development of atherosclerotic coronary and peripheral arterial disease [ 3 , 4 ]. It has been reported that changes in the balance of hydrogen sulfide (H 2 S) play an important role in the pathogenesis of β-cell dysfunction that occurs in response to T1DM and T2DM [ 5 , 6 ]. H 2 S is synthesized by mammalian tissues, and it serves various important regulatory functions [ 7 , 8 , 9 ].…”