Oral Glucose Tolerance and Tryptophan Metabolism in Non-Obese and Non-Insulin-Dependent Diabetic Goto–Kakizaki Rats Fed High-Tryptophan Diets

Abstract

SummaryWe investigated oral glucose tolerance and tryptophan (Trp) metabolism in non-obese and non-insulin-dependent diabetic Goto-Kakizaki (GK) rats fed high-Trp diets. Five-week-old male Wistar and GK rats were fed a 20% casein diet (control diet) or the same diet supplemented with 1%, 2%, 3%, or 5% Trp for 58 d. Oral glucose tolerance tests were performed on Days 14 and 28 of the experimental period. Urine as well as livers and blood were collected on the last day of the experiment. The glucose concentration and the amount of Trp metabolites were measured. On Day 14 of the experiment, the incremental blood glucose concentrations integrated over a period of 2 h (DAUC0-2h) of blood glucose in rats fed the 3% and 5% Trp diets had decreased by 13% and 18%, respectively, compared with that of the control-GK rats. However, no significant differences were found in the rats fed 11% or 12% Trp diets compared with control-GK rats. On Day 28, there were no significant differences found in the DAUC0-2h of blood glucose levels in any group including the control-GK group. On the last day, the concentrations of plasma glucose, total cholesterol, and triglyceride did not show differences in any group. There were no specific phenomena observed in the metabolism of Trp in GK rats even when fed an excess of Trp, compared with that of Wistar rats. Oral Trp administration and its continuous use may not improve blood glucose levels in type 2 diabetic rats. Key Words GK rat, tryptophan metabolism, glucose tolerance, diabetes, excessive tryptophan Nicotinamide (Nam), serotonin, and melatonin are important bioactive compounds derived from the essential amino acid, tryptophan (Trp) (1-3). Several studies have demonstrated that Trp can regulate physiological processes and may be the basis for novel therapeutics to prevent or treat chronic diseases (4).Previously, it was shown that plasma Trp levels in diabetic rats and children with insulin-dependent diabetes were significantly lower than normal (5-7). Recently, metabolome analysis demonstrated that plasma concentrations of Trp and its metabolite kynurenine were lower in type 2 diabetic Torii rats than in normal rats (7). It is known that Trp deficiency modulates glucose tolerance (8). Lower concentrations of Trp in blood lead to lower concentrations of serotonin, which could contribute to depression in diabetes (6).Data on Trp intake and blood glucose concentrations in diabetic conditions are limited. In the two reports published, oral administration of Trp did not modify glycemia in type 2 diabetic rats (9) and oral administration of Trp suppressed the elevation of blood glucose concentration in type 2 diabetic rats when the rats were glucose-loaded (10). Based on these results, we hypothesized that a single intravenous injection of Trp suppresses blood glucose concentration, whereas oral intake of Trp over several days will not influence glucose concentration in diabetic rats. Previously, we demonstrated that the Trp-Nam conversion ratio was significantly lower in streptozotocin-ind...

Impaired nicotinamide adenine dinucleotide (NAD+) metabolism in diabetes and diabetic tissues: Implications for nicotinamide‐related compound treatment

“…and others found that the conversion ratio of tryptophan to nicotinamide was lower in streptozotocin‐ and alloxan‐induced diabetes, suggesting that de novo synthesis of NAD + from tryptophan appears to be impaired. This phenomenon was not observed in a type 2 diabetes model; Goto‐Kakizaki rats 104 .…”

A High-Tryptophan Diet Reduces Seizure-Induced Respiratory Arrest and Alters the Gut Microbiota in DBA/1 Mice

“…Alteration of dietary TRP is often used as a non-invasive method to manipulate the TRP levels of the body, thereby affecting 5-HT neurotransmission in the CNS ( 39 ). HTD has been applied in the treatment of fatty liver disease ( 40 ), diabetes ( 41 ), Alzheimer's disease ( 42 ), and so on, which indicates that HTD may be safe and feasible as an adjunctive therapy. Our study is the first to demonstrate that HTD is an effective diet intervention in preventing SUDEP in DBA/1 mice.…”

The Gut Microbiota Mediates the Inhibition of Seizure-induced Respiratory Arrest in DBA/1 Mice fed a High Tryptophan Diet

“…Alteration of dietary TRP is often used as a noninvasive method to manipulate the TRP levels of the body, thereby affecting 5-HT neurotransmission in the CNS [37]. HTD has been applied in the treatment of fatty liver disease [38], diabetes [39], Alzheimer's disease [40] and so on, which indicates that HTD is safe and feasible as an adjunctive therapy. Our study is the rst to demonstrate that HTD is an effective diet intervention in preventing SUDEP in DBA/1 mice.…”