A major loss in islet mass and b-cell function precedes hyperglycemia in mice given multiple low doses of streptozotocin

V. Bonnevie-Nielsen, M. W. Steffes, A. Lernmark

Research output: Contribution to journalArticle

98 Citations (Scopus)

Abstract

Streptozotocin (SZ) given in five low doses causes diabetes and an associated lymphocytic infiltration of the pancreatic islets. Using C57BL/KsJ-mice, we demonstrate a reduction in islet number (-38%) and volume (-64%) within 1 day following the last injection of SZ. A substantial fall of insulin secretory capacity (-84%) in the in vitro perfused pancreas matches the reduction in islet cell volume. The parameters of decreased islet function seem to precede the peak of lymphocytic infiltration, occurring 3 days after the last dose of SZ. These functional changes are readily demonstrable before a rise in fasting blood glucose, but they seem to be reflected more readily by a rise in nonfasting blood glucose levels. With development of overt diabetes, as measured by elevated fasting and nonfasting glucose levels, the measures of islet volume and function are reduced to levels only 1-2% of those found in control mice. Taken together, these observations reflect a rapid, islet-toxic effect of SZ that substantially decreases insulin secretory capacity. When islet function falls more than 90%, blood glucose levels begin to reflect the pathophysiologic process. In many aspects, the low-dose SZ model of diabetes parallels the development of diabetes in man. If so, measures other than blood sugar must be developed to identify at an early stage processes reducing islet volume and function.

Original languageEnglish (US)
Pages (from-to)424-429
Number of pages6
JournalDiabetes
Volume30
Issue number5
DOIs
StatePublished - Jan 1 1981

Fingerprint

Streptozocin
Hyperglycemia
Blood Glucose
Islets of Langerhans
Fasting
Insulin
Experimental Diabetes Mellitus
Poisons
Inbred C57BL Mouse
Cell Size
Pancreas
Glucose
Injections

Cite this

A major loss in islet mass and b-cell function precedes hyperglycemia in mice given multiple low doses of streptozotocin. / Bonnevie-Nielsen, V.; Steffes, M. W.; Lernmark, A.

In: Diabetes, Vol. 30, No. 5, 01.01.1981, p. 424-429.

Research output: Contribution to journalArticle

@article{25f5da80cb7d4c0ab204557034f9aaa6,
title = "A major loss in islet mass and b-cell function precedes hyperglycemia in mice given multiple low doses of streptozotocin",
abstract = "Streptozotocin (SZ) given in five low doses causes diabetes and an associated lymphocytic infiltration of the pancreatic islets. Using C57BL/KsJ-mice, we demonstrate a reduction in islet number (-38{\%}) and volume (-64{\%}) within 1 day following the last injection of SZ. A substantial fall of insulin secretory capacity (-84{\%}) in the in vitro perfused pancreas matches the reduction in islet cell volume. The parameters of decreased islet function seem to precede the peak of lymphocytic infiltration, occurring 3 days after the last dose of SZ. These functional changes are readily demonstrable before a rise in fasting blood glucose, but they seem to be reflected more readily by a rise in nonfasting blood glucose levels. With development of overt diabetes, as measured by elevated fasting and nonfasting glucose levels, the measures of islet volume and function are reduced to levels only 1-2{\%} of those found in control mice. Taken together, these observations reflect a rapid, islet-toxic effect of SZ that substantially decreases insulin secretory capacity. When islet function falls more than 90{\%}, blood glucose levels begin to reflect the pathophysiologic process. In many aspects, the low-dose SZ model of diabetes parallels the development of diabetes in man. If so, measures other than blood sugar must be developed to identify at an early stage processes reducing islet volume and function.",
author = "V. Bonnevie-Nielsen and Steffes, {M. W.} and A. Lernmark",
year = "1981",
month = "1",
day = "1",
doi = "10.2337/diab.30.5.424",
language = "English (US)",
volume = "30",
pages = "424--429",
journal = "Diabetes",
issn = "0012-1797",
publisher = "American Diabetes Association Inc.",
number = "5",

}

TY - JOUR

T1 - A major loss in islet mass and b-cell function precedes hyperglycemia in mice given multiple low doses of streptozotocin

AU - Bonnevie-Nielsen, V.

AU - Steffes, M. W.

AU - Lernmark, A.

PY - 1981/1/1

Y1 - 1981/1/1

N2 - Streptozotocin (SZ) given in five low doses causes diabetes and an associated lymphocytic infiltration of the pancreatic islets. Using C57BL/KsJ-mice, we demonstrate a reduction in islet number (-38%) and volume (-64%) within 1 day following the last injection of SZ. A substantial fall of insulin secretory capacity (-84%) in the in vitro perfused pancreas matches the reduction in islet cell volume. The parameters of decreased islet function seem to precede the peak of lymphocytic infiltration, occurring 3 days after the last dose of SZ. These functional changes are readily demonstrable before a rise in fasting blood glucose, but they seem to be reflected more readily by a rise in nonfasting blood glucose levels. With development of overt diabetes, as measured by elevated fasting and nonfasting glucose levels, the measures of islet volume and function are reduced to levels only 1-2% of those found in control mice. Taken together, these observations reflect a rapid, islet-toxic effect of SZ that substantially decreases insulin secretory capacity. When islet function falls more than 90%, blood glucose levels begin to reflect the pathophysiologic process. In many aspects, the low-dose SZ model of diabetes parallels the development of diabetes in man. If so, measures other than blood sugar must be developed to identify at an early stage processes reducing islet volume and function.

AB - Streptozotocin (SZ) given in five low doses causes diabetes and an associated lymphocytic infiltration of the pancreatic islets. Using C57BL/KsJ-mice, we demonstrate a reduction in islet number (-38%) and volume (-64%) within 1 day following the last injection of SZ. A substantial fall of insulin secretory capacity (-84%) in the in vitro perfused pancreas matches the reduction in islet cell volume. The parameters of decreased islet function seem to precede the peak of lymphocytic infiltration, occurring 3 days after the last dose of SZ. These functional changes are readily demonstrable before a rise in fasting blood glucose, but they seem to be reflected more readily by a rise in nonfasting blood glucose levels. With development of overt diabetes, as measured by elevated fasting and nonfasting glucose levels, the measures of islet volume and function are reduced to levels only 1-2% of those found in control mice. Taken together, these observations reflect a rapid, islet-toxic effect of SZ that substantially decreases insulin secretory capacity. When islet function falls more than 90%, blood glucose levels begin to reflect the pathophysiologic process. In many aspects, the low-dose SZ model of diabetes parallels the development of diabetes in man. If so, measures other than blood sugar must be developed to identify at an early stage processes reducing islet volume and function.

UR - http://www.scopus.com/inward/record.url?scp=0019410914&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0019410914&partnerID=8YFLogxK

U2 - 10.2337/diab.30.5.424

DO - 10.2337/diab.30.5.424

M3 - Article

VL - 30

SP - 424

EP - 429

JO - Diabetes

JF - Diabetes

SN - 0012-1797

IS - 5

ER -