Insulin Metabolism and Degradation*

Duckworth, William C.; Kitabchi, Abbas E.

doi:10.1210/edrv-2-2-210

Cited by 201 publications

(107 citation statements)

References 238 publications

Supporting

Mentioning

101

Contrasting

Order By: Relevance

“…Consistent with this concept, in vitro studies reveal that insulin-receptor internalization and reinsertion into the plasma membrane in hepatocytes can be entrained to insulin pulses delivered at a physiological frequency (36). While a major proportion of insulin is completely removed by the liver after internalization of the insulin-receptor complex, some amounts of insulin can be released back into the circulation after hepatocyte receptor binding or internalization (37). Therefore, it is possible that some insulin bound to the hepatocytes during an insulin wavefront reenters the circulation during the subsequent period of low insulin secretion.…”

Section: Discussionmentioning

confidence: 82%

“…Written informed consent was obtained from all study participants. Five healthy subjects (two men and three women) mean age 32 years (range [25][26][27][28][29][30][31][32][33][34][35][36][37][38][39], with a mean BMI of 24.9 kg/m 2 (21.2-27.1) participated. All subjects were nondiabetic based on fasting plasma glucose concentration (mean fasting plasma glucose 5.4 mmol/l [5.1-5.8]) and HbA 1c values (mean 4.8% [4.5-5.0]).…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Pulsatile Insulin Secretion Dictates Systemic Insulin Delivery by Regulating Hepatic Insulin Extraction In Humans

2005

View full text Add to dashboard Cite

In health, insulin is secreted in discrete pulses into the portal vein, and the regulation of the rate of insulin secretion is accomplished by modulation of insulin pulse mass. Several lines of evidence suggest that the pattern of insulin delivery by the pancreas determines hepatic insulin clearance. In previous large animal studies, the amplitude of insulin pulses was related to the extent of insulin clearance. In humans (and in large animals), the amplitude of insulin oscillations is ϳ100-fold higher in the portal vein than in the systemic circulation, despite only a fivefold dilution, implying preferential hepatic extraction of insulin pulses. In the present study, by direct hepatic vein sampling in healthy humans, we sought to establish the extent of first-pass hepatic insulin extraction and to determine whether the pattern of insulin secretion (insulin pulse mass and amplitude) dictates the hepatic insulin clearance and thereby delivery of insulin to extrahepatic insulin-responsive tissues.

show abstract

Section: Discussionmentioning

confidence: 82%

Section: Methodsmentioning

confidence: 99%

Pulsatile Insulin Secretion Dictates Systemic Insulin Delivery by Regulating Hepatic Insulin Extraction In Humans

2005

View full text Add to dashboard Cite

show abstract

“…On the other hand, reproducing the physiological route of intraportal insulin delivery might favor this approach, which would putatively expose hepatocytes directly to secreted insulin via fenestrated sinusoids. Binding of insulin to the hepatocyte receptors results in rapid internalization of the insulin-receptor complex, subsequent initiation of the intracellular insulin signaling cascades, and proteolytic degradation of the internalized insulin molecules (30). By these means, the liver acts as the primary insulinresponsive organ and serves as a safeguard against systemic hyperinsulinemia.…”

Section: Discussionmentioning

confidence: 99%

Intrahepatic Transplanted Islets in Humans Secrete Insulin in a Coordinate Pulsatile Manner Directly Into the Liver

et al. 2006

View full text Add to dashboard Cite

Intrahepatic islet transplantation is an experimental therapy for type 1 diabetes. In the present studies, we sought to address the following questions: 1) In humans, do intrahepatic transplanted islets reestablish coordinated puslatile insulin secretion? and 2) To what extent is insulin secreted by intrahepatic transplanted islets delivered to the hepatic sinusoids (therefore effectively restoring a portal mode of insulin delivery) versus delivered to the hepatic central vein (therefore effectively providing a systemic form of insulin delivery)? To address the first question, we examined insulin concentration profiles in the overnight fasting state and during a hyperglycemic clamp (ϳ150 mg/dl) in 10 recipients of islet transplants and 10 control subjects. To address the second question, we measured first-pass hepatic insulin clearance in two recipients of islet autografts after pancreatectomy for pancreatitis versus five control subjects by direct catheterization of the hepatic vein. We report that coordinate pulsatile insulin secretion is reestablished in islet transplant recipients and that glucose-mediated stimulation of insulin secretion is accomplished by amplification of insulin pulse mass. Direct hepatic catheterization studies revealed that intrahepatic islets in humans do deliver insulin directly to the hepatic sinusoid because ϳ80% of the insulin is extracted during first pass. In conclusion, intrahepatic islet transplantation effectively restores the liver to pulsatile insulin delivery.

show abstract

“…Binding of hormone to the insulin receptor initiates signals responsible for biologic actions. One component of the mechanisms underlying deactivation of the biologic response is degradation of the ligand (32)(33)(34)(35). One may speculate that processes that bypass hormone degradation will most likely iend to preserve or maintain biologic effects, and cells process HPro in ways that can potentially preserve biologic responsiveness.…”

Section: Column Fractionsmentioning

confidence: 99%

Endocytotic uptake, processing, and retroendocytosis of human biosynthetic proinsulin by rat fibroblasts transfected with the human insulin receptor gene.

Levy¹,

Ullrich²,

Olefsky³

1988

J. Clin. Invest.

View full text Add to dashboard Cite

show abstract

Insulin Metabolism and Degradation*

Cited by 201 publications

References 238 publications

Pulsatile Insulin Secretion Dictates Systemic Insulin Delivery by Regulating Hepatic Insulin Extraction In Humans

Pulsatile Insulin Secretion Dictates Systemic Insulin Delivery by Regulating Hepatic Insulin Extraction In Humans

Intrahepatic Transplanted Islets in Humans Secrete Insulin in a Coordinate Pulsatile Manner Directly Into the Liver

Endocytotic uptake, processing, and retroendocytosis of human biosynthetic proinsulin by rat fibroblasts transfected with the human insulin receptor gene.

Contact Info

Product

Resources

About