Butyrate and type 1 diabetes mellitus: can we fix the intestinal leak?

Abstract

OBJECTIVES:

An intestinal permeability defect precedes type 1 diabetes mellitus and may be a permissive factor in its pathogenesis. Butyrate strengthens the intestinal tight junctions. We hypothesized that enteral administration of sodium butyrate (NaB) in preweaned rats would result in differences in the development of diabetes associated with decreased inflammation and pancreatic β-cell destruction.

MATERIALS AND METHODS:

Using biobreeding diabetes-prone rat pups, oral NaB or saline was administered twice per day via micropipette from postnatal days 10 to 23. Rat pups were randomly assigned to 1 of 4 groups for the first experiment (control group, n = 7) and 3 different doses of butyrate groups (n = 8 for each group) and 2 groups for the second and third experiments (control n = 23; NaB at 400 mg · kg(-1) · day(-1), n = 20). Animals were studied into adulthood (up to day 140) for development of diabetes.

RESULTS:

The results showed that the survival rates were 28% versus 20% (butyrate vs control). No significant differences in survival were seen; however, there was a trend of delaying of onset of diabetes in the butyrate group. There were no differences of pancreatic histology score of islet inflammation between the 2 groups. Cytokine-induced neutrophil chemoattractant-1 was lower in the butyrate group at a dose of 400 mg · kg(-1) · day(-1) in the distal small intestine (P = 0.008) and in the liver (P = 0.01). There were no significant differences in the tracer flux measurements across the distal ileum and colon between the 2 animal groups.

CONCLUSIONS:

Oral NaB given during the preweaning period did not significantly decrease the subsequent development of death from diabetes in biobreeding diabetes-prone rats.

• Authors: Nan Li, Marguerite Hatch, Clive H Wasserfall, Martha Douglas-Escobar, Mark A Atkinson, Desmond A Schatz, Josef Neu
• Journal: Journal of pediatric gastroenterology and nutrition (J Pediatr Gastroenterol Nutr) Vol. 51 Issue 4 Pg. 414-7 (Oct 2010) ISSN: 1536-4801 [Electronic] United States
• PMID: 20706153 (Publication Type: Journal Article)

Chemical References

• Butyrates
• Chemokine CXCL1
• Cxcl1 protein, rat
• Cytokines
• Sodium Chloride

Topics

• Administration, Oral
• Animals
• Butyrates (administration & dosage)
• Chemokine CXCL1 (drug effects)
• Cytokines (drug effects, metabolism)
• Diabetes Mellitus, Type 1 (complications, metabolism)
• Dose-Response Relationship, Drug
• Inflammation (complications, metabolism)
• Insulin-Secreting Cells (drug effects)
• Intestinal Diseases (complications, metabolism)
• Intestinal Mucosa (drug effects, metabolism)
• Intestines (drug effects)
• Liver (drug effects, metabolism)
• Permeability (drug effects)
• Rats
• Rats, Inbred BB
• Sodium Chloride (administration & dosage)
• Survival Rate