Islets in alginate macrobeads reverse diabetes despite minimal acute insulin secretory responses.

Abstract:

BACKGROUND:Encapsulation of islets has been widely investigated as a treatment for diabetes. The characteristics and dynamics of insulin secretion by encapsulated islets in response to glucose and other secretagogues are not well understood. METHODS:In our study, macroencapsulated syngeneic islets at 3-4 wk after transplantation were studied for insulin release in response to i.v. glucose (hyperglycemic clamps at 250 or 350 mg/dl plasma glucose), arginine (i.v. bolus, 100 mg/kg), glucagon-like peptide-1 (i.v. infusion for 20 min, 2.2 pmol/kg/min), and meal challenge. Syngeneic islets (6000 islets) were encapsulated in alginate macrobeads (2-3 mm diameter) with or without poly-L-lysine coating and transplanted into the peritoneal cavity of STZ-diabetic Lewis rats. Normal (nontransplanted) and diabetic Lewis rats transplanted with "naked" islets under the kidney capsule served as controls. RESULTS:Animals transplanted with macrobeads displayed subnormal insulin responses to glucose, arginine, and glucagon-like peptide-1 despite achieving normoglycemia faster than animals with renal subcapsular islet transplants. Plasma insulin responses to meal challenges were blunted in animals with macrobeads resulting in increased plasma glucose excursions. CONCLUSIONS:We conclude that, after transplantation into diabetic Lewis rats, macroencapsulated islets have significantly impaired insulin secretion despite achieving normal fed glycemic levels.

journal_name

Transplantation

journal_title

Transplantation

authors

Trivedi N,Keegan M,Steil GM,Hollister-Lock J,Hasenkamp WM,Colton CK,Bonner-Weir S,Weir GC

doi

10.1097/00007890-200101270-00006

subject

Has Abstract

pub_date

2001-01-27 00:00:00

pages

203-11

issue

2

eissn

0041-1337

issn

1534-6080

journal_volume

71

pub_type

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