Sodium Butyrate Ameliorates Streptozotocin-Induced Type 1 Diabetes in Mice by Inhibiting the HMGB1 Expression

Abstract

Type 1 diabetes (T1D) is an autoimmune disease characterized by the immune cell-mediated progressive destruction of pancreatic β-cells. High-mobility group box 1 protein (HMGB1) has been recognized as a potential immune mediator to enhance the development of T1D. So we speculated that HMGB1 inhibitors could have anti-diabetic effect. Sodium butyrate is a short fatty acid derivative possessing anti-inflammatory activity by inhibiting HMGB1. In the current study, we evaluated the effects of sodium butyrate in streptozotocin (STZ)-induced T1D mice model. Diabetes was induced by multiple low-dose injections of STZ (40 mg/kg/day for 5 consecutive days), and then sodium butyrate (500 mg/kg/day) was administered by intraperitoneal injection for 7 consecutive days after STZ treatment. Blood glucose, incidence of diabetes, body weight, pancreatic histopathology, the amounts of CD4+T cell subsets, IL-1β level in serum and pancreatic expressions levels of HMGB1, and NF-κB p65 protein were analyzed. The results showed that sodium butyrate treatment decreased blood glucose and serum IL-1β, improved the islet morphology and decreased inflammatory cell infiltration, restored the unbalanced Th1/Th2 ratio, and down-regulated Th17 to normal level. In addition, sodium butyrate treatment can inhibit the pancreatic HMGB1 and NF-κB p65 protein expression. Therefore, we proposed that sodium butyrate should ameliorate STZ-induced T1D by down-regulating NF-κB mediated inflammatory signal pathway through inhibiting HMGB1.

MHC II-PI3K/Akt/mTOR Signaling Pathway Regulates Intestinal Immune Response Induced by Soy Glycinin in Hybrid Grouper: Protective Effects of Sodium Butyrate

“…In addition, IL-1β can stimulate T-type immune cells to differentiate and produce IFN-γ. In mice, SB may inhibit pro-inflammatory response by downregulating IL-1β ( 39 ). IL-1β may be decreased by SB for ischemic stroke in middle-aged female rats ( 40 ).…”

Butyrate alleviates diabetic kidney disease by mediating the miR‐7a‐5p/P311/TGF‐β1 pathway

“…Butyrate is a metabolite produced as a result of fermentation by the microbiota and has been reported to play a protective role against diabetes and some types of kidney diseases. 6,7,9 However, the specific function and mechanism of butyrate in the renal fibrosis of db/db mice and HG-induced SV40-MES-13 cells has not been studied. Db/db mice have a mutation deletion of the leptin receptor and are common models used for studying type II diabetes.…”

“…[6][7][8] Intraperitoneal injection of butyrate alleviated streptozotocin (STZ)-induced mice pancreatic injury by inhibiting the pancreatic HMGB1 and NF-κB p65 protein expression. 9 Besides, intraperitoneal injection of NaBu (sodium butyrate) (500 mg/kg/day) also ameliorated transforming growth factor-β1 (TGF-β1)-induced fibrosis and inflammation in the kidneys of STZ-induced diabetic rats. 10 Dong's study also reported that a diet containing NaBu (5 g/kg/day) alleviates albuminuria and mesangial matrix expansion by activating Nrf2 in STZ-induced diabetic mice.…”

Suppression of HDAC2 by sodium butyrate alleviates apoptosis of kidney cells in db/db mice and HG‑induced NRK‑52E cells

“…Xu et al (8) found that oral NaBu administration significantly alleviates inflammation in db/db mice by correcting intestinal microecological disorder and protecting intestinal barrier integrity. Additionally, intraperitoneal injection of NaBu alleviates streptozotocin (STZ)-induced mice pancreatic injury and inflammatory responses by downregulating the NF-κB pathway (9).…”