Therapies for inter-relating diabetes and obesity – GLP-1 and obesity

Abstract

The incretin impairment, which seems to exist in both obesity and diabetes, may link these two pathologies and underlines the potential of GLP-1-based therapies in the prevention and treatment of these diseases.

Incretin-based therapies for obesity treatment

“…However, it is unclear whether peripherally released GLP-1 needs to enter the brain to affect food intake, or whether other routes of action are involved on feeding behavior [19]. Therefore, weight loss seems to be resulting from combined central and peripheral actions of GLP-1 receptor agonists, collectively promoting satiety, decreasing hunger sensation and ultimately leading to reductions in food intake [19,51].…”

Liraglutide: A Review of Its Use in the Management of Obesity

“…One pharmacological strategy involves targeting the incretin hormone glucagon-like peptide-1 (GLP-1). GLP-1 is a gut derived hormone released from L cells after food intake and exhibits pleiotropic effects throughout the body, including physiological regulation of appetite and calorie intake; GLP-1 levels are reduced in obese patients [11][12][13][14].…”

“…GLP-1 may act indirectly via stimulation of intestinal vagal afferents, with subsequent actions at satiation centres in the CNS, but also may act directly by entering the brain via the circumventrilcular organs (a region where peptides from the peripheral circulation are not blocked by the blood-brain barrier) to activate CNS nuclei involved in satiation [11][12][13][14][15]. Evidence from animal studies suggests that weight lowering effects of liraglutide are primarily mediated through central effects, specifically via GLP-1 receptors on arcuate nucleus neurons expressing propiomelanocortin (POMC)/cocaineand amphetamine-regulated transcript (CART) [16].…”

“…Like endogenous GLP-1, liraglutide binds to and activates the GLP-1 receptor, a cell-surface receptor coupled to adenyl cyclase activation via the stimulatory G-protein Gs [11][12][13][14]. GLP-1 receptors are widely distributed throughout the body, including in the pancreas, stomach, intestine, lung, kidney, heart, peripheral nervous system and CNS [19].…”

“…GLP-1 receptors are widely distributed throughout the body, including in the pancreas, stomach, intestine, lung, kidney, heart, peripheral nervous system and CNS [19]. Activation of GLP-1 receptors triggers several responses, including glucose-dependent stimulation of pancreatic insulin secretion and inhibition of pancreatic glucagon secretion (glucoregulatory effects) and regulation of appetite and calorie intake [11][12][13][14]. This section focuses on the effects of liraglutide in reducing bodyweight.…”