Non-catch-up growth in intrauterine growth-retarded rats showed glucose intolerance and increased expression of PDX-1 mRNA

Pediatr Int. 2011 Apr;53(2):181-6. doi: 10.1111/j.1442-200X.2010.03204.x.

Abstract

Background: Children born with intrauterine growth retardation (IUGR) show long-term complications like non-catch-up growth and type 2 diabetes. We hypothesize that the duration of malnutrition influences the growth and pancreatic development in IUGR. The pancreatic duodenal homeobox-1 (PDX-1) expression might also be different because it links glucose metabolism to the regulation of insulin gene transcription in the pancreas.

Methods: We made an IUGR rat model with a low-protein diet (8% casein) during gestational periods. Catch-up rats (CU) were given normal lab chow immediately after birth. Non-catch-up rats (NCU) were given normal lab chow after lactation periods. PDX-1 mRNA level, islet areas and intravenous glucose tolerance test (IVGTT) were assessed in each group and compared with control rats (C) at the 16th week.

Results: The weight and length of CU and C rats were not different after 3 weeks, while NCU rats were smaller than C and CU rats (P < 0.05). In IVGTT, the 20-min and 50-min glucose level and area under the curve for glucose were increased in NCU rats compared with those values in C and CU rats (P < 0.05). The islet area of NCU rats was smaller than that of C and CU rats (P < 0.05). In contrast, PDX-1 mRNA levels of NCU rats were higher than those of C rats (P < 0.05). CU rats showed normal glucose response in IVGTT with increased islet number and size.

Conclusions: IUGR rats that failed to undergo catch-up growth might be prone to abnormal glucose tolerance, decreased islet size, and increased PDX-1 mRNA levels in early adult life.

MeSH terms

  • Animals
  • Body Weight
  • Diabetes Mellitus, Type 2 / etiology
  • Diabetes Mellitus, Type 2 / physiopathology
  • Diet, Protein-Restricted
  • Disease Models, Animal
  • Female
  • Fetal Growth Retardation / epidemiology
  • Fetal Growth Retardation / metabolism*
  • Fetal Growth Retardation / physiopathology
  • Glucose Intolerance / complications
  • Glucose Tolerance Test
  • Growth
  • Homeodomain Proteins / metabolism*
  • Insulin Resistance / physiology
  • Islets of Langerhans Transplantation / pathology
  • Lactation
  • Male
  • Malnutrition / therapy
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Wistar
  • Trans-Activators / metabolism*

Substances

  • Homeodomain Proteins
  • RNA, Messenger
  • Trans-Activators
  • pancreatic and duodenal homeobox 1 protein