glucagon-like-peptide-1 and Organophosphate-Poisoning

Higher incidence of diabetes along with increased use of pesticides is seen in Southeast Asia. Recent hypothesis postulated a link between acetylcholinesterase inhibitor insecticides and type 2 diabetes through the GLP-1 pathway. This study compares the GLP-1 response between groups with low and high red blood cell acetylcholinesterase (RBC-AChE) activity. A comparative cross-sectional study was conducted amongst patients who were within 3 months after an acute organophosphate or carbamate poisoning (acute group) and amongst vegetable farmers with low (chronic group) and high (control group) RBC-AChE activity. Acute (366 mU/μM Hb) and chronic (361 mU/μM Hb) groups had significantly lower RBC-AChE activity in comparison to the control (471 mU/μM Hb) group (P < 0.0001). Only the acute group, which has had atropine therapy, showed a significantly lower 120 min value in comparison to the control group (P = 0.0028). Also, the acute group had significantly low late (P = 0.0287) and total (P = 0.0358) responses of GLP-1 in comparison to the control group. The findings of the study allude towards attenuation of GLP-1 response amongst patients after acute organophosphate and carbamate poisoning. The possibility of an atropine-mediated attenuation of GLP-1 response was discussed.

Topics: Acetylcholinesterase; Acute Disease; Adult; Atropine; Carbamates; Chronic Disease; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Erythrocytes; Female; Glucagon-Like Peptide 1; Humans; Incidence; Incretins; Insecticides; Male; Middle Aged; Occupational Exposure; Organophosphate Poisoning; Sri Lanka

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.

Topics: Acetylcholine; Acetylcholinesterase; Animals; Atropine; Diabetes Mellitus, Type 2; Endocrine System; Glucagon-Like Peptide 1; Glucose; Homeostasis; Humans; Incretins; Models, Theoretical; Organophosphate Poisoning; Organophosphates; Treatment Outcome