Myocardial infarction is sufficient to increase GLP‐1 secretion, leading to improved left ventricular contractility and mitochondrial respiratory capacity

Abstract

Myocardial infarction causes rapid impairment of left ventricular function and requires a hypercontractile response of non-infarcted tissue areas to maintain haemodynamic stability. This compensatory adaptation is mediated by humoral, inflammatory and neuronal signals. GLP-1 is an incretin hormone with glucoregulatory and cardioprotective capacities and is secreted in response to nutritional and inflammatory stimuli. Inactivation of GLP-1 is caused by the ubiquitously present enzyme DPP-4. In this study, circulating concentrations of GLP-1 were assessed after myocardial infarction and were evaluated in the light of metabolism, left ventricular contractility and mitochondrial function. Circulating GLP-1 concentrations were markedly increased in patients with acute myocardial infarction. Experimental myocardial infarction by permanent LAD ligation proved sufficient to increase GLP-1 secretion in mice. This took place in a time-dependent manner, which coincided with the capacity of DPP-4 inhibition, by linagliptin, to augment left ventricular contractility in a GLP-1 receptor-dependent manner. Mechanistically, DPP-4 inhibition increased AMPK activity and stimulated the mitochondrial respiratory capacity of non-infarcted tissue areas. We describe a new functional relevance of inflammatory GLP-1 secretion for left ventricular contractility during myocardial infarction.

Mechanisms of early glucose regulation disturbance after out-of-hospital cardiopulmonary resuscitation: An explorative prospective study

“…Elevated GLP-1 levels during critical illness have been reported by previous studies [10,11,18]. These studies reported a 1.4- to 8-fold increase in GLP-1 levels and a 2- to 10-fold increase in IL-6 levels within 30 minutes to 6 hours depending on the study design [10,11,18].…”

“…GLP-1 is an incretin hormone that causes insulin secretion and suppresses glucagon production in the body [22]. Previous studies have shown that endogenous GLP-1 levels increase during critical illness, preceded by an early rise of IL-6 levels, and this independently predicts mortality [10,11,18,23]. Increased endogenous GLP-1 seems to be beneficial.…”

“…GLP-1 analysis for prehospital and hospital admission samples was performed using an ELISA test (Human GLP-1 ELISA, BioVendor, Brno, Czech Republic) according to the manufacturer’s instructions. The laboratory reference values for the concentrations were as follows: insulin 10–20 mU/l, glucagon <209 ng/ml, GLP-1 1–2 ng/ml, and IL-6 <3.4 ng/l [9–11].…”

Peptide YY (PYY) Is Associated with Cardiovascular Risk in Patients with Acute Myocardial Infarction

“…Secretion of PYY happens in response to nutritional stimuli from enteroendocrine L-cells located in the distal gut. The same cell population produces GLP-1 in response to nutritional but also inflammatory stimuli, leading to elevated GLP-1 levels in patients with acute myocardial infarction or sepsis [4,31]. Importantly, GLP-1 was found to be an excellent and independent predictor for future cardiovascular events or mortality in both groups of patients, demonstrating a relevant interaction between the cardiovascular system and the gut [5,32].…”

“…Recent studies have identified gastrointestinal hormones as modulators of cardiovascular risk. The gut-derived peptide GLP-1 was found to be secreted in response to acute myocardial infarction and to independently predict adverse outcome in this patient population [4,5]. Importantly, GLP-1 receptor agonists reduced cardiovascular events in high-risk patients with diabetes [6][7][8][9].…”