A Non-Obese Hyperglycemic Mouse Model that Develops after Birth with Low Birthweight

Abstract

The number of low birthweight (LBW) infants weighing below 2500 g has not decreased in Japan. This study aimed to develop an adult non-obese hyperglycemic mouse model born with LBW to study the pathogenesis. At 16.5 days of gestation, transient intrauterine ischemia (blocked blood flow in both uterine arteries for 15 min) was performed in a subgroup of pregnant mice (group I). Non-occluded dams were used as sham controls (group C). After birth, female pups in each group were weaned at 4 weeks of age and reared on the normal diet until 8 weeks of age (n = 7). Fasting blood glucose levels, serum immunoreactive insulin (IRI), and body composition were then measured. Metabolite analyses was performed on the liver tissues. Birthweight was significantly lower in group I compared with group C. Pups from group I remained underweight with low fat-free mass and showed hyperglycemia with high serum IRI and homeostasis model assessment of insulin resistance levels, indicating insulin resistance. Metabolite analyses showed significantly reduced adenosine triphosphate and nicotinamide adenine dinucleotide production and increased lactic acid in group I. The pathogenesis of our non-obese hyperglycemic mouse model may be due to increased myogenic insulin resistance based on mitochondrial dysfunction and reduced lean body mass.

Amelioration of Insulin Resistance by Whey Protein in a High-Fat Diet-Induced Pediatric Obesity Male Mouse Model

“…Therefore, merely adding whey protein to regular nutrition could increase protein intake and potentially be counterproductive concerning future risks of diabetes, obesity, and other diseases. We plan to conduct whey protein intervention experiments using the low-birth-weight, non-obese hyperglycemic mouse model developed by Katayama et al [ 53 ] to assess the potential of whey protein in enhancing glycolipid metabolism. In our previous studies, we administered only whey protein or casein protein.…”

Efficacy of Human Recombinant Growth Hormone in Females of a Non-Obese Hyperglycemic Mouse Model after Birth with Low Birth Weight

“…A factor contributing to the pathogenesis of hyperglycemia in the non-obese hyperglycemic mouse model is the impaired mitochondrial function and increased myogenic insulin resistance caused by oxidative stressors [ 12 ]. In this study, we investigated whether GH administration could ameliorate the increase in myogenic insulin resistance.…”

“…Mitochondrial function is impaired by oxidative stressors [ 43 , 44 ]. In particular, oxidative stress-induced mitochondrial dysfunction occurs in a non-obese hyperglycemic mouse model after birth with LBW [ 12 ]. The Ischemia-GH group showed decreased oxidative stressors and increased antioxidants compared to the Ischemia group.…”

“…We selected the non-obese hyperglycemic mouse model after birth with LBW as a model for non-obese T2DM [ 12 ]. Female mice from this model were chosen referencing the findings of Urakami [ 10 ].…”

“…Female mice from this model were chosen referencing the findings of Urakami [ 10 ]. In this model, Katayama et al reported that mitochondrial dysfunction induced by oxidative stress reduces lean body mass and triggers myogenic insulin resistance [ 12 ]. We have decided to administer growth hormone (GH) to the non-obese hyperglycemic mouse model after birth with LBW to prevent the reduction in lean body mass.…”