Mechanism of Insulin Release From Islets of Langerhans in a Rat Model of Normal Infants and Infants of Diabetic Mothers

Neonatal hypoglycemia is common in infants of diabetic mothers (IDM). The hypoglycemia is believed to result from persistent insulin hypersecretion due to the elevated glucose concentration in utero. The mechanism for the hypersecretion of insulin is not known. The glucose sensing mechanism in the fetal and neonatal IDM and normal control rats was investigated. Pregnant rats were given an i.p. injection of streptozotocin (65 mg/kg) on day 13 of pregnancy to induce diabetes mellitus. Offspring were evaluated on days $-$1, 1, 2, 5 and 10 of life. Parameters measured were body weight, plasma glucose and insulin, in vitro glucose-stimulated insulin release, and protein expression of GLUT1, GLUT2, and glucokinase by immunocytochemistry in the isolated islet and Western blot on the whole pancreas. The IDM had significantly lower mean body weights at all ages studied (p $<$ 0.01, n $\ge$ 34); significantly higher mean plasma glucose concentration at day $-$1 (p $<$ 0.0001, n $\ge$ 181) and significantly lower mean plasma glucose at all neonatal ages (p $<$ 0.01, n $\ge$ 36). Mean plasma insulin was significantly lower at all ages except for day 10 of life (p $<$ 0.05, n $\ge$ 26). The IDM group mean for the in vitro glucose-stimulated insulin release data was significantly greater than controls (p $<$ 0.0001, n $\ge$ 4). The insulin release in the IDM was significantly higher on specific days: day $-$1 at glucose concentration of 11.1 and 22.2 mmol/L (p $<$ 0.05, n $\ge$ 4); day 1 at glucose concentration of 5.5 mmol/L (p $<$ 0.05, n = 6 experiments); and day 2 at glucose concentration of 11.1 mmol/L 22.2 mmol/L (p $<$ 0.05, n $\ge$ 6). By immunocytochemistry, the IDM had greater GLUT1 protein expression on days 1, 2, and 5 (n = 5 replicates); greater GLUT2 expression on days $-$1, 1, and 5 (n = 7 replicates); and greater glucokinase expression on days 1, 2, and 10 (n = 4 replicates). Western blot data revealed significantly lower GLUT2 protein expression in the IDM on days $-$1 and 2 (p $<$ 0.05, n = 4). These data confirm the elevated insulin release in IDM and suggest that glucose transporter and glucokinase proteins involved in glucose sensing are altered in the IDM.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Nutritional Sciences

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2015

Author dc:creator

• Sullivan, Debra Kay

Contributors dc:contributor

• Reynolds, Robert D.

• Biology, Animal Physiology

Language dc:language

eng

Identifier

(MiAaPQ)AAI9812782

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/84977