Hepatic glycogen metabolism and insulin receptor status after long-term peripheral insulin delivery in the islet-transplanted diabetic rat

Diabetes ◽  
1986 ◽  
Vol 35 (3) ◽  
pp. 306-310 ◽  
Author(s):  
Y. T. Kruszynska ◽  
P. D. Home ◽  
L. Agius ◽  
K. G. Alberti
2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Jingbo Yang ◽  
Yanjun Li ◽  
Rui Ye ◽  
Ying Zheng ◽  
Xiangling Li ◽  
...  

AbstractThe incidence rate of diabetes has been increasing every year in nearly all nations and regions. The traditional control of diabetes using transdermal insulin delivery by metal needles is generally associated with pain and potential infections. While microneedle arrays (MAs) have emerged as painless delivery techniques, the integration of MA systems with electronic devices to precisely control drug delivery has rarely been realized. In this study, we developed an iontophoresis-microneedle array patch (IMAP) powered by a portable smartphone for the active and controllable transdermal delivery of insulin. The IMAP in situ integrates iontophoresis and charged nanovesicles into one patch, achieving a one-step drug administration strategy of “penetration, diffusion and iontophoresis”. The MA of the IMAP is first pressed on the skin to create microholes and then is retracted, followed by the iontophoresis delivery of insulin-loaded nanovesicles through these microholes in an electrically controlled manner. This method has synergistically and remarkably enhanced controlled insulin delivery. The amount of insulin can be effectively regulated by the IMAP by applying different current intensities. This in vivo study has demonstrated that the IMAP effectively delivers insulin and produces robust hypoglycemic effects in a type-1 diabetic rat model, with more advanced controllability and efficiency than delivery by a pristine microneedle or iontophoresis. The IMAP system shows high potential for diabetes therapy and the capacity to provide active as well as long-term glycemic regulation without medical staff care.


1999 ◽  
Vol 31 (4) ◽  
pp. 656-663 ◽  
Author(s):  
Lukas Krähenbühl ◽  
Bruno Hagenbuch ◽  
Simona Berardi ◽  
Markus Schäfer ◽  
Stephan Krähenbühl

Diabetes ◽  
2002 ◽  
Vol 51 (1) ◽  
pp. 49-54 ◽  
Author(s):  
M. G. Bischof ◽  
E. Bernroider ◽  
M. Krssak ◽  
M. Krebs ◽  
H. Stingl ◽  
...  

Diabetologia ◽  
2016 ◽  
Vol 59 (12) ◽  
pp. 2702-2710 ◽  
Author(s):  
Sabela Diaz-Castroverde ◽  
Selene Baos ◽  
María Luque ◽  
Marianna Di Scala ◽  
Gloria González-Aseguinolaza ◽  
...  

1975 ◽  
Vol 97 (3) ◽  
pp. 266-275
Author(s):  
R. N. Bergman ◽  
M. El Refai

The survival of mammals is dependent upon a relatively constant, adequate supply of glucose to the central nervous system, despite large fluctuations in the amount of food available. When food is abundant, the liver stores ingested carbohydrate as glycogen, and during fasts, the stored glycogen is released at a precisely regulated rate to maintain the blood glucose level. The rates of storage and release of carbohydrate by the liver are determined by the plasma concentrations of several bloodborne signals; most important are the concentrations of glucose, and the hormones insulin and glucagon. To understand the complex control relationships of these three signals as they affect the liver, their individual dynamic influences have been determined experimentally, and they have been integrated by means of a computer simulation of the pathways of hepatic glycogen metabolism. The simulation studies have led to specific hypotheses about the biochemical effects of glucose and insulin on the liver. The simulation studies have also led to the conclusion that glucose exerts a rapid moment-to-moment influence of glucose on the rate of uptake of glucose by the liver. Insulin, however, by exerting a slower influence on the sensitivity of the liver to glucose, is very effective in “optimizing” the amount of glycogen which the liver stores food during food intake. Thus, integrated experimental and simulation studies can lead to a view of a physiological regulating system which does not emerge from either approach used alone.


2015 ◽  
Vol 119 (6) ◽  
pp. 663-669 ◽  
Author(s):  
Yi-Yuan Lin ◽  
Shin-Da Lee ◽  
Chia-Ting Su ◽  
Tsung-Lin Cheng ◽  
Ai-Lun Yang

Dysfunction of insulin and insulin-like growth factor-1 (IGF-1) is associated with the pathophysiology of hypertension. The influence of long-term exercise on vascular dysfunction caused by hypertension remains unclear. We investigated whether long-term treadmill training improved insulin- and IGF-1-mediated vasorelaxation in hypertensive rats. Eight-week-old male spontaneously hypertensive rats (SHR) were randomly divided into sedentary and exercise (SHR-EX) groups. The SHR-EX group was trained on a treadmill for 60 min/day, 5 days/wk, for 8 wk. Wistar-Kyoto rats (WKY) were used as the normal control group. After training, aortic insulin- and IGF-1-mediated vasorelaxation was evaluated in organ baths. Additionally, the roles of phosphatidylinositol 3-kinase (PI3K), nitric oxide synthase (NOS), and aortic protein expression were examined in the three groups. Compared with sedentary SHR and WKY groups, insulin- and IGF-1-mediated vasorelaxation was significantly enhanced to a nearly normal level in the SHR-EX group. After endothelial denudation, blunted and comparable vasorelaxation was found among the three groups. Pretreatment with selective PI3K and NOS inhibitors attenuated insulin- and IGF-1-mediated vasorelaxation, and no significant difference was found among the three groups after the pretreatment. The aortic protein levels of the insulin receptor (IR), IGF-1 receptor (IGF-1R), insulin receptor substrate-1 (IRS-1), and endothelial NOS (eNOS) were also significantly increased in the SHR-EX group compared with the other two groups. These results suggested that treadmill training elicited the amelioration of endothelium-dependent insulin/IGF-1-mediated vasorelaxation partly via the increased activation of PI3K and NOS, as well as the enhancement of protein levels of IR, IGF-1R, IRS-1, and eNOS, in hypertension.


2000 ◽  
Vol 32 ◽  
pp. 123 ◽  
Author(s):  
C. Lang ◽  
C. Seiler ◽  
A. Zimmermann ◽  
S. Krähenbühl ◽  
L. Krähenbühl

1977 ◽  
Vol 74 (2) ◽  
pp. 231-241 ◽  
Author(s):  
YVONNE MANGNALL ◽  
ANNE SMYTHE ◽  
D. N. SLATER ◽  
GILLIAN R. MILNER ◽  
R. D. G. MILNER ◽  
...  

Intraperitoneal transplantation of collagenase-digested, isogeneic, neonatal rat pancreatic tissue successfully reversed streptozotocin-induced diabetes in 77% of recipients. The low serum immunoreactive insulin, hyperglycaemia, glycosuria and weight loss, characteristic of the diabetic animal, were corrected and the reduced activities of hepatic glucokinase and pyruvate kinase, and the low glycogen concentration of the liver of diabetic rats were restored to normal. Forty-three per cent of the successfully transplanted rats became normoglycaemic within 1 month of transplantation whereas 57% took from 1 to 6 months to achieve normoglycaemia and displayed a mild glucose intolerance when subjected to a glucose load. The rats which had not become normoglycaemic 6 months after transplantation showed some amelioration of the diabetic state, as shown by increased serum immunoreactive insulin and hepatic glycogen concentration and a slow weight gain compared with diabetic controls.


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