Islets in alginate macrobeads reverse diabetes despite minimal acute insulin secretory responses.
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.
Trivedi
N
N
Section of Islet Transplantation and Cell Biology, Joslin Diabetes Center, Boston, MA 02215, USA.
Keegan
M
M
Steil
G M
GM
Hollister-Lock
J
J
Hasenkamp
W M
WM
Colton
C K
CK
Bonner-Weir
S
S
Weir
G C
GC
D000464:Alginates / Q000008:administration & dosage*; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight / Q000502:physiology; D002214:Capsules / Q000008:administration & dosage*; D003920:Diabetes Mellitus / Q000473:pathology / Q000628:therapy*; D004435:Eating; D005215:Fasting; D015309:Glucose Clamp Technique; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000166:cytology* / Q000473:pathology; D008297:Male; D051381:Rats; D011917:Rats, Inbred Lew
D000464:Alginates; D001786:Blood Glucose; D002214:Capsules; D007328:Insulin