Relationship between growth retardation and impaired glucose tolerance in hypothyroidal growth-retarded (grt) mice

Growth-retarded (grt) mice exhibit congenital hypothyroidism and a characteristic growth pause followed by delayed onset of pubertal growth. This pattern of growth has never been reported in any other animal model exhibiting hypothyroidism; therefore, the growth retardation observed in grt mice is unlikely to be explained completely by the low plasma thyroid hormone levels. As growth is closely related to nutrient metabolism, we investigated the relationship between the appearance of growth retardation and glucose utilization, which is the main component of nutrient metabolism, in the peripubertal stage of grt mice. The relative weights of the organs involved in nutrient digestion and absorption were abnormal in grt mice. The intraperitoneal glucose tolerance test (IGTT) showed impaired glucose tolerance in grt mice. Moreover, this symptom appeared in parallel with the progression of growth retardation in grt mice. The impaired blood glucose levels on the IGTT in grt mice were considered to be attributable to decreased plasma insulin levels rather than to impaired insulin sensitivity. The pattern of anti-insulin antibody staining on sections of pancreatic islets from grt mice was almost the same as that in the corresponding sections from normal mice. Insulin treatment accelerated the growth of peripubertal grt mice. These findings suggest that the appearance of growth retardation in grt mice might be partially attributable to a reduction in glucose metabolism and impairment of insulin secretion during the early period of growth.