Improvement of glucose tolerance with immunomodulators on type 2 diabetic animals.
Cytokine-inducers prevent insulin-dependent diabetes mellitus (IDDM) in animal models. We extend this therapy to non-insulin-dependent diabetes mellitus (NIDDM), because it was reported that diabetes of KK-Ay mice, a model for NIDDM, was recovered by allogenic bone-marrow transplantation that also prevented IDDM in animal models. An i.p. or i.v. injection of streptococcal preparation (OK-432) lowered fasting blood glucose (FBG) levels and markedly improved glucose tolerance test (GTT) in KK-Ay mice for more than 32 h regardless of the glucose loading routes (oral, i.v. or i.p.), while an i.v. injection of BCG improved FBG and GTT for more than 4 wks without body weight loss. The improvement of FBG and GTT with OK-432 was brought about in other NIDDM animals, GK rats and Wistar fatty rats. Among various cytokines possibly induced by OK-432 and BCG, IL-1 alpha, TNF alpha and lymphotoxin significantly improved FBG and GTT in KK-Ay mice, whereas IL-2 and IFN gamma did not. There were no differences between the OK-432-treated KK-Ay mice and control in histology of the pancreas, degree of insulin-induced decrease in blood glucose levels, and muscle glycogen synthase activities. As to insulin secretion, there is a tendency that the OK-432-treatment less that 1 week did not affect insulin levels during GTT, whereas the treatment more than 2 weeks increased the insulin levels. Thus, cytokine-inducers improved FBG and glucose tolerance of NIDDM animals probably via cytokines. The results imply a role of the cytokines in glucose tolerance of NIDDM, although precise immune and metabolic mechanisms remain to be elucidated.
Zhu
X P
XP
Third Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
Satoh
J
J
Muto
G
G
Muto
Y
Y
Sagara
M
M
Takahashi
K
K
Seino
H
H
Hirai
S
S
Masuda
T
T
Tanaka
S
S
Ishida
H
H
Seino
Y
Y
Toyota
T
T
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000378:metabolism*; D005951:Glucose Tolerance Test; D006006:Glycogen Synthase / Q000378:metabolism; D007328:Insulin / Q000097:blood / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D010844:Picibanil / Q000494:pharmacology*; D051381:Rats; D011920:Rats, Inbred WF
D000276:Adjuvants, Immunologic; D001786:Blood Glucose; D007328:Insulin; D010844:Picibanil; D006006:Glycogen Synthase