Tryptophan in the Serotonergic Control of Pancreatic Functions in Stress: Implications for type 2 Diabetes

¹Neuroscience Research Laboratory, Dr Panjwani Center for Molecular Medicine & Drug Research (PCMD), International Center for Chemical and Biological Science (ICCBS), University of Karachi, Karachi 75270, Pakistan

²Department of Biochemistry, Neurochemistry and Neuropharmacology Research Laboratory, University of Karachi, Karachi 75270, Pakistan

*Corresponding author: Prof. Dr. Darakhshan Jabeen Haleem, Dr Panjwani Center for Molecular Medicine & Drug Research (PCMD), International Center for Chemical and Biological Science (ICCBS), University of Karachi, Karachi 75270, Pakistan, Phone: +92 3022274695, E-mails: [email protected]; [email protected]

Received Date : March 26, 2024

Publication Date: May 22, 2024

Citation: Haleem DJ. (2024). Tryptophan in the Serotonergic Control of Pancreatic Functions in Stress: Implications for type 2 Diabetes. Nutraceutical Res. 3(1):7.

Copyright: Haleem DJ. © (2024).

ABSTRACT

Type 2 diabetes (T2D), a metabolic disorder, is highly prevalent in every society and people of every economic status are affected. Stress related epigenetic factors are known to increase risk for diabetes. Treatment response of this lifelong metabolic disorder highly depends on comorbid conditions, which worsens the treatment outcome and increases mortality. Novel, comorbidity related, drug targets for treating diabetes are therefore highly needed. In this context, a role of serotonin (5-hydroxytryptamine; 5-HT), a biogenic amine seems important. Acting centrally, serotonin is implicated in a number of stress related mental illnesses. The synthesis of serotonin also occurs intracellularly in the pancreatic beta cells, where it is co-localized with insulin and regulates serotonylation-dependent insulin secretion. In addition, serotonin present in the blood circulation can also modulate insulin release from beta cells through autocrine and paracrine signals. The synthesis of serotonin depends upon the availability of its precursor tryptophan, which is an essential amino acid. Tryptophan obtained from dietary proteins is largely utilized via hepatic kynurenine pathway. Evidence suggests that stress-induced sustained increases of circulating glucocorticoid (GCs) can further enhance utilization of tryptophan via kynurenine pathway; the availability of tryptophan for serotonin synthesis is therefore decreased. This article targets effects of stress-induced sustained increases of GCs on circulating tryptophan and intracellular serotonin in the pancreatic beta cells and suggests that together with blood glucose levels, circulating levels of serotonin, tryptophan and kynurenine should be considered as biochemical markers for therapeutic intervention in diabetes.

Keywords: Pancreas, Stress, Serotonin, Diabetes, Glucocorticoids, Tryptophan, Kynurenine