Intrahepatic transplanted islets in humans secrete insulin in a coordinate pulsatile manner directly into the liver.

Abstract

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 ( approximately 150 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 approximately 80% of the insulin is extracted during first pass. In conclusion, intrahepatic islet transplantation effectively restores the liver to pulsatile insulin delivery.

• Authors: Juris J Meier, Irene Hong-McAtee, Ryan Galasso, Johannes D Veldhuis, Antoinette Moran, Bernhard J Hering, Peter C Butler
• Journal: Diabetes (Diabetes) Vol. 55 Issue 8 Pg. 2324-32 (Aug 2006) ISSN: 0012-1797 [Print] United States
• PMID: 16873697 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Blood Glucose
• C-Peptide
• Insulin
• Glucose

Topics

• Adult
• Blood Glucose (analysis)
• C-Peptide (blood)
• Diabetes Mellitus, Type 1 (surgery)
• Fasting
• Female
• Glucose (pharmacology)
• Glucose Clamp Technique
• Hepatic Veins
• Humans
• Insulin (blood, metabolism)
• Insulin Secretion
• Islets of Langerhans (drug effects, metabolism)
• Islets of Langerhans Transplantation
• Liver
• Male
• Middle Aged
• Pancreatectomy
• Pancreatitis (surgery)
• Periodicity