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Preserved insulin secretion and insulin independence in recipients of islet autografts.
N Engl J Med. 1992 Jul 23; 327(4):220-6.NEJM

Abstract

BACKGROUND

Transplantation of pancreatic islets, rather than whole pancreas, has been introduced as a treatment for diabetes mellitus. We studied five patients ranging in age from 12 to 37 years who had severe chronic pancreatitis for which they underwent total pancreatectomy followed by isolation and hepatic transplantation of their own islets.

METHODS

All patients had remained insulin-independent for 1 to 7 1/2 years after transplantation. The numbers of islets transplanted ranged from 110,000 to 412,000. Islet function was assessed by measuring the plasma insulin responses to intravenous glucose and arginine and the plasma glucagon responses to hypoglycemia and arginine. In one patient, islet function was studied during catheterization of the hepatic vein, portal vein, and splenic artery and by analysis of a liver-biopsy specimen.

RESULTS

After transplantation, the mean (+/- SD) fasting plasma glucose concentration was 122 +/- 47 mg per deciliter (6.8 +/- 2.6 mmol per liter) and the hemoglobin A1c concentration was 6.0 +/- 0.8 percent in the five patients. The values were most abnormal--214 mg per deciliter (11.9 mmol per liter) and 7.3 percent, respectively--in the patient who received only 110,000 islets. The acute plasma insulin responses to glucose and to arginine in the five patients were 23 +/- 13 and 26 +/- 10 microU per milliliter (168 +/- 94 and 184 +/- 70 pmol per liter), respectively, as compared with 58 +/- 6 and 37 +/- 8 microU per milliliter (416 +/- 44 and 267 +/- 61 pmol per liter) in the normal subjects. The peak plasma glucagon responses to insulin and arginine were 21 +/- 4 and 65 +/- 36 pg per milliliter, respectively, as compared with 125 +/- 28 and 156 +/- 99 pg per milliliter in the normal subjects. All five patients had plasma epinephrine but not pancreatic polypeptide responses to hypoglycemia. The results of the hepatic-vein catheterization in one patient indicated that the transplanted islets released insulin and glucagon in response to arginine. Immunoperoxidase staining of this patient's liver-biopsy specimen showed that the islets contained insulin, glucagon, and somatostatin but not pancreatic polypeptide.

CONCLUSIONS

Intrahepatic transplantation of as few as 265,000 islets can result in the release of insulin and glucagon at appropriate times and in prolonged periods of insulin independence.

Authors+Show Affiliations

Pyzdrowski KL
Diabetes Center, University of Minnesota, Minneapolis 55455.
Kendall DM
No affiliation info available
Halter JB
No affiliation info available
Nakhleh RE
No affiliation info available
Sutherland DE
No affiliation info available
Robertson RP
No affiliation info available

MeSH

AdolescentAdultArginineBlood GlucoseChronic DiseaseFemaleGlucagonGlucoseGlycated HemoglobinHumansHypoglycemiaInsulinInsulin SecretionIslets of LangerhansIslets of Langerhans TransplantationLiverMalePancreatectomyPancreatic PolypeptidePancreatitisTransplantation, Autologous

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

1614463

Citation

Pyzdrowski, K L., et al. "Preserved Insulin Secretion and Insulin Independence in Recipients of Islet Autografts." The New England Journal of Medicine, vol. 327, no. 4, 1992, pp. 220-6.
Pyzdrowski KL, Kendall DM, Halter JB, et al. Preserved insulin secretion and insulin independence in recipients of islet autografts. N Engl J Med. 1992;327(4):220-6.
Pyzdrowski, K. L., Kendall, D. M., Halter, J. B., Nakhleh, R. E., Sutherland, D. E., & Robertson, R. P. (1992). Preserved insulin secretion and insulin independence in recipients of islet autografts. The New England Journal of Medicine, 327(4), 220-6.
Pyzdrowski KL, et al. Preserved Insulin Secretion and Insulin Independence in Recipients of Islet Autografts. N Engl J Med. 1992 Jul 23;327(4):220-6. PubMed PMID: 1614463.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Preserved insulin secretion and insulin independence in recipients of islet autografts. AU - Pyzdrowski,K L, AU - Kendall,D M, AU - Halter,J B, AU - Nakhleh,R E, AU - Sutherland,D E, AU - Robertson,R P, PY - 1992/7/23/pubmed PY - 1992/7/23/medline PY - 1992/7/23/entrez SP - 220 EP - 6 JF - The New England journal of medicine JO - N Engl J Med VL - 327 IS - 4 N2 - BACKGROUND: Transplantation of pancreatic islets, rather than whole pancreas, has been introduced as a treatment for diabetes mellitus. We studied five patients ranging in age from 12 to 37 years who had severe chronic pancreatitis for which they underwent total pancreatectomy followed by isolation and hepatic transplantation of their own islets. METHODS: All patients had remained insulin-independent for 1 to 7 1/2 years after transplantation. The numbers of islets transplanted ranged from 110,000 to 412,000. Islet function was assessed by measuring the plasma insulin responses to intravenous glucose and arginine and the plasma glucagon responses to hypoglycemia and arginine. In one patient, islet function was studied during catheterization of the hepatic vein, portal vein, and splenic artery and by analysis of a liver-biopsy specimen. RESULTS: After transplantation, the mean (+/- SD) fasting plasma glucose concentration was 122 +/- 47 mg per deciliter (6.8 +/- 2.6 mmol per liter) and the hemoglobin A1c concentration was 6.0 +/- 0.8 percent in the five patients. The values were most abnormal--214 mg per deciliter (11.9 mmol per liter) and 7.3 percent, respectively--in the patient who received only 110,000 islets. The acute plasma insulin responses to glucose and to arginine in the five patients were 23 +/- 13 and 26 +/- 10 microU per milliliter (168 +/- 94 and 184 +/- 70 pmol per liter), respectively, as compared with 58 +/- 6 and 37 +/- 8 microU per milliliter (416 +/- 44 and 267 +/- 61 pmol per liter) in the normal subjects. The peak plasma glucagon responses to insulin and arginine were 21 +/- 4 and 65 +/- 36 pg per milliliter, respectively, as compared with 125 +/- 28 and 156 +/- 99 pg per milliliter in the normal subjects. All five patients had plasma epinephrine but not pancreatic polypeptide responses to hypoglycemia. The results of the hepatic-vein catheterization in one patient indicated that the transplanted islets released insulin and glucagon in response to arginine. Immunoperoxidase staining of this patient's liver-biopsy specimen showed that the islets contained insulin, glucagon, and somatostatin but not pancreatic polypeptide. CONCLUSIONS: Intrahepatic transplantation of as few as 265,000 islets can result in the release of insulin and glucagon at appropriate times and in prolonged periods of insulin independence. SN - 0028-4793 UR - https://www.unboundmedicine.com/medline/citation/1614463/Preserved_insulin_secretion_and_insulin_independence_in_recipients_of_islet_autografts_ DB - PRIME DP - Unbound Medicine ER -