Mammalian metabolism of erythritol: a predictive biomarker of metabolic dysfunction
CURRENT OPINION IN CLINICAL NUTRITION AND METABOLIC CARE
Authors: Ortiz, Semira R.; Field, Martha S.
Abstract
Purpose of review To summarize recent advances in our understanding of mammalian erythritol metabolism and its use as a predictive biomarker of cardiometabolic disease risk. Recent findings Elevated serum erythritol predicts future central adiposity gain and type 2 diabetes mellitus in healthy adults. Erythritol is a newly recognized human metabolic product of glucose, synthesized through the pentose phosphate pathway. The final conversion of this metabolic pathway is catalyzed by the enzymes sorbitol dehydrogenase and alcohol dehydrogenase 1. Erythritol is also a well characterized nonnutritive sweetener. Recent studies show that dietary erythritol can be metabolized to erythrose or erythronate in humans before excretion. Elevated serum erythritol predicts risk for cardiometabolic disease, but more research is required to maximize its utility as a biomarker, including characterizing the determinants of endogenous erythritol synthesis from glucose. New insights into dietary erythritol metabolism also highlight the need to evaluate the effects of long-term erythritol consumption.
A novel thrombin-based triagonist with diabetes-protective and weight-lowering potential
LIFE SCIENCES
Authors: Zhang, Jingyu; Zhang, Zhenyu; Ma, Cong; Zeng, Li; Zhang, Ying; Wang, Peng; Xu, Lijuan
Abstract
Aims: To investigate the diabetes-protective effect and weight-lowering potential of a novel long-acting triagonist at three metabolically related hormone receptors including glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), glucagon receptors. Main methods: Triagonist were designed in an iterative manner from native GLP-1, GIP and Glucogan. Main peptide chain (termed TG peptides) and subsequently modified LTG peptides were synthesized via solid phase synthesis. In vitro receptor activity assay was performed to screen the TG peptide with most balanced potency on all three receptors. The in vitro biological activities of modified TG peptides were further investigated by albumin-binding measurement and proteolytic cleavage test. Subsequently, oral glucose tolerance test (OGTT), pharmacokinetic test and chronic study were subjected to the acute and long-term efficacy evaluation of selected fusion peptide, LTG-6. Key findings: TG-8 exhibited equally aligned constituent efficacy and supraphysiological potency on corresponding receptor without cross-reactivity. Modified TG-8, termed LTG-6, exerted the great binding affinity for human serum albumin and the enhanced rational controlled-release of TG-8 in vitro. Further OGTT in different gene knockout mice and diabetic mice demonstrated the promising hypoglycemic and insulinotropic abilities of LTG-6. After long-term treatment for 8 weeks, LTG-6 was proved superior to co-agonists to decrease the body weight and %HbA1c, improve reverse dyslipidemia and glycemic control in the DIO models. Significance: LTG-6, as a newly designed long-acting triagonist, holds potential to correct the obesity related metabolic disorders.