title: From organophosphate poisoning to diabetes mellitus: The incretin effect.
abstract: Organophosphate (OP) poisoning induced disruption of glucose homeostasis is well established. OP poisoning leads to accumulation of acetylcholine (ACh) due to the inhibition of acetylcholinesterases (AChE). On the other hand the incidence of type 2 diabetes mellitus (T2DM) is shown to rise along with the use of pesticides in Southeast Asia. Attenuation of the 'incretin effect' is seen in T2DM. This effect is regulated by a complex loop of mechanism involving ACh driven muscarinic receptors. We hypothesize that OP poisoning leads to disruption of glucose homeostasis by attenuation of the incretin effect. Inhibition of the Glucagon Like Peptide-1 (GLP-1) secretion is our main focus of interest. Positive finding of the hypothesis will open possibility of using incretin based treatment modalities to treat or prevent acute OP induced disruption of glucose homeostasis.
authors.affiliation: Department of Pharmacology, Faculty of Medicine and Allied Sciences, Rajarata University of Sri Lanka, Saliyapura, Anuradhapura, Sri Lanka. Electronic address: rathishdeva@gmail.com.
authors.forename: D
authors.initials: D
authors.lastname: Rathish
authors.affiliation: Department of Community Medicine, Faculty of Medicine and Allied Sciences, Rajarata University of Sri Lanka, Saliyapura, Anuradhapura, Sri Lanka.
authors.forename: S B
authors.initials: SB
authors.lastname: Agampodi
authors.affiliation: Department of Pharmacology, Faculty of Medicine and Allied Sciences, Rajarata University of Sri Lanka, Saliyapura, Anuradhapura, Sri Lanka.
authors.forename: M A C S
authors.initials: MACS
authors.lastname: Jayasumana
authors.affiliation: Department of Medicine, Faculty of Medicine and Allied Sciences, Rajarata University of Sri Lanka, Saliyapura, Anuradhapura, Sri Lanka.
authors.forename: S H
authors.initials: SH
authors.lastname: Siribaddana
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D001285:Atropine / Q000627:therapeutic use; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000517:prevention & control*; D004703:Endocrine System; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D054795:Incretins / Q000378:metabolism*; D008962:Models, Theoretical; D062025:Organophosphate Poisoning / Q000188:drug therapy*; D010755:Organophosphates / Q000633:toxicity; D016896:Treatment Outcome
chemical_list: D054795:Incretins; D010755:Organophosphates; D001285:Atropine; D052216:Glucagon-Like Peptide 1; D000110:Acetylcholinesterase; D005947:Glucose; D000109:Acetylcholine
keywords: Acetylcholine; Atropine; Glucagon Like Peptide-1; Glucose homeostasis; Incretins; Organophosphate; Type 2 diabetes mellitus