Hector Warnes’ comment on Despoina Asanaglou et al.’s 2021 paper, “Dopamine regulates pancreatic glucagon and insulin secretion via adrenergic and dopaminergic receptors”

       This is outstanding research combining both basic sciences and clinical observations. I was not aware that dopamine is a modulator of glucagon and insulin secretion via its action on both adrenergic and dopaminergic receptors in human and mouse pancreatic islets. For years we have observed that patients treated with antipsychotic compounds such as olanzapine, clozapine and  haloperidol (singled out by the researchers) developed weight gain, insulin resistance and higher risk of having Diabetes type 2. The authors in meticulous research demonstrated in humans and rodents the underpinnings of this "metabolic syndrome." The precursor of dopamine is L-DOPA which causes hyper-glycemia in both human and rodent pancreatic islets (beta cells D1 R and D3 R). It was further shown that the antipsychotic compounds increase pancreatic insulin and glucagon secretion in pancreatic islet cells alpha and beta, disinhibit insulin release leading to increased secreted insulin over time signaling and elevating glucagon release. Eventually inducing hyper-glycemia which further exacerbates insulin resistance.

       A couple of points arise after reading this excellent paper:

1. What is the mechanism of weight gain commonly seen in patients treated with anti-psychotic agents? Independently of the use of anti-psychotic drugs, type 2 Diabetes are usually preceded by obesity and by imbalance of the ghrelin-leptin hormones that regulate appetite and food intake (Makris, Alexandrou, Papatsoutsos et al. 2017).

2. An elaboration on the established association between severe depression preceding pancreatic adenocarcinoma in over 50% of patients would be informative (Carney and Jones 2003).

References:

Aslanoglou D, Bertera S, Sánchez-Soto M, Free RB, Lee J, Zong W, Xue X, Shrestha S, Brissova M, Logan RW, Wollheim CB, Trucco M, Yechoor VK, Sibley DR, Bottino R, Freyberg Z. Dopamine regulates pancreatic glucagon and insulin secretion via adrenergic and dopaminergic receptors. Transl Psychiatry 2021;11(1):59. 

Carney CP, Jones L. Relationship between Depression and Pancreatic Cancer in the general Population. Psychosomatic Med 2003;65(5):884-8.  

Makris CM, Alexandrou A, Papatsoutsos EG, Malietzis G, Tsilimigras DI, Guerron AD, Moris D. Ghrelin and Obesity: identifying gaps and dispelling myths. A reappraisal. In Vivo 2017;31(6):1047-50.

June 10, 2021