title: Islet transplantation and insulin administration relieve long-term complications and rescue the residual endogenous pancreatic β cells.
abstract: Islet transplantation is a poorly investigated long-term strategy for insulin replacement and for treatment of complications in patients with diabetes. We investigated whether islet transplantation and insulin treatment can relieve diabetic neuropathy and rescue the residual endogenous pancreatic β cells. We used a multimodal approach, with five groups of Sprague-Dawley rats studied for 8 months: control rats, diabetic rats, insulin-treated diabetic rats with moderate or mild hyperglycemia, and diabetic rats transplanted with microencapsulated islets. Islet transplantation normalized glycemia and increased body and muscle weight; it was also effective in reducing proteinuria and altered liver function. Transplantation significantly improved tail nerve conduction velocity, Na(+)-K(+)-ATPase activity, and morphological alterations in the sciatic nerve as evidenced by decrease in g-ratio; it also restored thermal and ameliorated mechanical nociceptive thresholds. Morphometric analysis of pancreas indicated a significant β-cell volume increase in transplanted rats, compared with mildly and moderately hyperglycemic rats. Thus, allogeneic islet transplantation had a positive systemic effect in diabetic rats and induced regression of the established neuropathy and restitution of the typical characteristics of the islets. These findings strongly reinforce the need for improving glycemic control, not only to reverse established diabetic complications but also to improve β-cell status in diabetic pancreas.
authors.affiliation: Department of Biomedical Engineering, Mario Negri Institute for Pharmacological Research, IRCCS-Institute for Research, Hospitalization, and Scientific Care, Bergamo, Italy. Electronic address: marina.figliuzzi@marionegri.it.
authors.forename: Marina
authors.initials: M
authors.lastname: Figliuzzi
authors.forename: Roberto
authors.initials: R
authors.lastname: Bianchi
authors.forename: Cristina
authors.initials: C
authors.lastname: Cavagnini
authors.forename: Raffaella
authors.initials: R
authors.lastname: Lombardi
authors.forename: Carla
authors.initials: C
authors.lastname: Porretta-Serapiglia
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Lauria
authors.forename: Federica
authors.initials: F
authors.lastname: Avezza
authors.forename: Annalisa
authors.initials: A
authors.lastname: Canta
authors.forename: Valentina
authors.initials: V
authors.lastname: Carozzi
authors.forename: Alessia
authors.initials: A
authors.lastname: Chiorazzi
authors.forename: Paola
authors.initials: P
authors.lastname: Marmiroli
authors.forename: Cristina
authors.initials: C
authors.lastname: Meregalli
authors.forename: Norberto
authors.initials: N
authors.lastname: Oggioni
authors.forename: Barbara
authors.initials: B
authors.lastname: Sala
authors.forename: Guido
authors.initials: G
authors.lastname: Cavaletti
authors.forename: Andrea
authors.initials: A
authors.lastname: Remuzzi
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D048909:Diabetes Complications / Q000097:blood / Q000473:pathology* / Q000503:physiopathology / Q000628:therapy*; D005934:Glucagon / Q000378:metabolism; D005951:Glucose Tolerance Test; D006943:Hyperglycemia / Q000150:complications / Q000473:pathology; D007328:Insulin / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000201:enzymology / Q000473:pathology*; D016381:Islets of Langerhans Transplantation; D008297:Male; D009431:Neural Conduction / Q000187:drug effects; D059225:Nociception / Q000187:drug effects; D017288:Pain Threshold / Q000187:drug effects; D011507:Proteinuria / Q000150:complications / Q000473:pathology; D051381:Rats; D011917:Rats, Inbred Lew; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D007328:Insulin; D017392:Thiobarbituric Acid Reactive Substances; D005934:Glucagon; D000254:Sodium-Potassium-Exchanging ATPase