High-fat diet induced insulin resistance in pregnant rats through pancreatic pax6 signaling pathway

Int J Clin Exp Pathol. 2015 May 1;8(5):5196-202. eCollection 2015.

Abstract

Objective: To explore the changes in pancreas islet function of pregnant rats after consumption of high-fat diet and the underlying mechanism.

Methods: Thirty pregnant Wistar rats were randomly divided into two groups: high-fat diet group and normal control group. Twenty days after gestation, fasting blood glucose concentration (FBG) and fasting serum insulin concentration (FINS) were measured. Then, oral glucose tolerance test (OGTT) and insulin release test (IRT) were performed. Finally, all the rats were sacrificed and pancreas were harvested. Insulin sensitivity index (ISI) and insulin resistance index (HOMA-IR) were calculated according to FBG and FINS. RT-PCR and Real-time PCR were performed to study the expression of paired box 6 transcription factor (Pax6) and its target genes in pancreatic tissues.

Results: The body weight was significantly increased in the high-fat diet group compared with that of normal control rats (P<0.05). The fasting plasma glucose of rats in high-fat diet group was significantly increased compared with that of normal control rats (6.62 mmol/L vs. 4.96 mmol/L, P<0.05), however there was no significant difference in fasting serum insulin concentration between the two groups. OGTT and IRT were abnormal in the high-fat diet group. The high-fat diet rats were more prone to impaired glucose tolerance and insulin resistance. The level of the expression of Pax6 transcription factor and its target genes in pancreas, such as pancreatic and duodenal homeobox factor-1 (Pdx1), v-maf musculoaponeurotic fibrosarcoma oncogene homolog A (MafA) and glucose transporter 2 (Glut2) were decreased significantly compared with those of normal control group.

Conclusion: High-fat diet feeding during pregnancy may induce insulin resistance in maternal rats by inhibiting pancreatic Pax6 and its target genes expression.

Keywords: Nutrition; gestation; insulin resistance; insulin resistance index; insulin sensitivity index; oral glucose tolerance test; pax6; rats.

MeSH terms

  • Animal Nutritional Physiological Phenomena
  • Animals
  • Biomarkers / blood
  • Blood Glucose / metabolism
  • Diabetes, Gestational / blood
  • Diabetes, Gestational / genetics
  • Diabetes, Gestational / metabolism*
  • Diet, High-Fat*
  • Disease Models, Animal
  • Eye Proteins / genetics
  • Eye Proteins / metabolism*
  • Female
  • Gene Expression Regulation
  • Glucose Tolerance Test
  • Glucose Transporter Type 2 / genetics
  • Glucose Transporter Type 2 / metabolism
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism*
  • Insulin / blood
  • Insulin Resistance*
  • Insulin-Secreting Cells / metabolism*
  • Maf Transcription Factors, Large / genetics
  • Maf Transcription Factors, Large / metabolism
  • Maternal Nutritional Physiological Phenomena
  • PAX6 Transcription Factor
  • Paired Box Transcription Factors / genetics
  • Paired Box Transcription Factors / metabolism*
  • Pregnancy
  • Rats, Wistar
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Signal Transduction*
  • Time Factors

Substances

  • Biomarkers
  • Blood Glucose
  • Eye Proteins
  • Glucose Transporter Type 2
  • Homeodomain Proteins
  • Insulin
  • Maf Transcription Factors, Large
  • PAX6 Transcription Factor
  • Paired Box Transcription Factors
  • Pax6 protein, rat
  • Repressor Proteins
  • Slc2a2 protein, rat