Effect of pancreas transplantation on decreased levels of circulating bone gamma-carboxyglutamic acid-containing protein and osteopenia in rats with streptozotocin-induced diabetes.
Diabetic osteopenia has been known as one of the chronic complications of diabetes mellitus, and a decrease in bone turnover has been thought to be one of the pathophysiological characteristics of this complication. In order to investigate the effect of long-term insulin therapy on low bone turnover in diabetes, pancreas transplantation was performed on streptozotocin-induced diabetic rats. Plasma levels of bone gamma-carboxyglutamic acid-containing protein(osteocalcin) in untreated diabetic rats were 0.9 +/- 0.1 (mean +/- SEM) nmol/l, significantly lower than the value of 4.2 +/- 0.6 nmol/l in control rats (p less than 0.01). Pancreas transplantation reversed this decrease to 6.3 +/- 1.1 nmol/l, which was not significantly different from the value in control rats. The circulating levels of calcitriol were significantly decreased in the untreated diabetic group (p less than 0.01), and the decrease was fully reversed by pancreas transplantation. In addition, the decreases in bone length, strength and weight were also improved by the transplantation. This evidence clearly shows that the improvement of metabolic derangements in diabetes by insulin is essential for the prevention of deterioration in diabetic osteopenia. It is possible, therefore, that insulin exerts an indirect beneficial influence through the metabolic amelioration on the decreases in bone turnover and circulating osteocalcin in diabetes mellitus, or has a direct stimulatory effect on the osteoblasts via the insulin receptor since its presence has been shown recently in osteoblastic cells.
Ishida
H
H
Department of Metabolism and Clinical Nutrition, Kyoto University School of Medicine, Japan.
Seino
Y
Y
Takeshita
N
N
Kurose
T
T
Tsuji
K
K
Okamoto
Y
Y
Someya
Y
Y
Hara
K
K
Akiyama
Y
Y
Imura
H
H
D015055:1-Carboxyglutamic Acid / Q000032:analysis; D000818:Animals; D001851:Bone Diseases, Metabolic / Q000209:etiology / Q000517:prevention & control*; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002117:Calcitriol / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000097:blood* / Q000378:metabolism / Q000601:surgery*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000378:metabolism; D007328:Insulin / Q000097:blood / Q000494:pharmacology; D008297:Male; D009929:Organ Size; D010006:Osteoblasts / Q000502:physiology / Q000648:ultrastructure; D015675:Osteocalcin / Q000032:analysis / Q000097:blood*; D016035:Pancreas Transplantation / Q000502:physiology*; D051381:Rats; D011917:Rats, Inbred Lew; D011972:Receptor, Insulin / Q000502:physiology; D013311:Streptozocin; D014807:Vitamin D / Q000378:metabolism
D007328:Insulin; D015675:Osteocalcin; D014807:Vitamin D; D015055:1-Carboxyglutamic Acid; D013311:Streptozocin; D011972:Receptor, Insulin; D002117:Calcitriol