Insulin replacement therapy in diabetic rats using an osmotic pump normalizes expression of enzymes key to hepatic carbohydrate metabolism

Ken Kramer, Bruce F. Giffin, James W. Fox, Richard L. Drake

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Intensively treating type I diabetics with continuous subcutaneous insulin infusions or multiple daily insulin injections to normalize mean blood glucose concentrations significantly reduces the onset of secondary diabetic complications when compared to conventionally treated diabetics. Our studies focused on characterizing hepatic enzyme expression in intensively and conventionally treated diabetic rats. Alloxan-induced diabetic rats were conventionally treated with insulin injected twice daily or intensively treated with similar daily dosages of insulin administered via a surgically implanted osmotic pump. Our results demonstrate a significant difference in hepatic enzyme expression when these treatment regimes are compared. In conventionally treated diabetic rats, phosphoenolpyruvate carboxykinase (PEPCK) protein and mRNA levels remained slightly elevated when compared to normal animals, glycogen phosphorylase (GP) protein levels were still slightly decreased, and glycogen synthase (GS) protein and mRNA levels remained at the elevated levels observed in untreated diabetics. In contrast, the protein and mRNA levels of all three enzymes were normalized in the insulin pump-treated animals. These results suggest that intensive insulin therapy improves glycemia directly by normalizing hepatic gene expression while conventional insulin therapy normalizes plasma glucose concentrations indirectly.

Original languageEnglish
Pages (from-to)291-297
Number of pages7
JournalArchives of Biochemistry and Biophysics
Volume368
Issue number2
DOIs
StatePublished - Aug 15 1999
Externally publishedYes

Fingerprint

Carbohydrate Metabolism
Rats
Pumps
Insulin
Liver
Enzymes
Messenger RNA
Therapeutics
Animals
Proteins
Glycogen Phosphorylase
Subcutaneous Infusions
Glycogen Synthase
Alloxan
Phosphoenolpyruvate
Diabetes Complications
Gene expression
Blood Glucose
Plasmas
Gene Expression

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Insulin replacement therapy in diabetic rats using an osmotic pump normalizes expression of enzymes key to hepatic carbohydrate metabolism. / Kramer, Ken; Giffin, Bruce F.; Fox, James W.; Drake, Richard L.

In: Archives of Biochemistry and Biophysics, Vol. 368, No. 2, 15.08.1999, p. 291-297.

Research output: Contribution to journalArticle

@article{a1e9a8909b0542f8b726dcafba891416,
title = "Insulin replacement therapy in diabetic rats using an osmotic pump normalizes expression of enzymes key to hepatic carbohydrate metabolism",
abstract = "Intensively treating type I diabetics with continuous subcutaneous insulin infusions or multiple daily insulin injections to normalize mean blood glucose concentrations significantly reduces the onset of secondary diabetic complications when compared to conventionally treated diabetics. Our studies focused on characterizing hepatic enzyme expression in intensively and conventionally treated diabetic rats. Alloxan-induced diabetic rats were conventionally treated with insulin injected twice daily or intensively treated with similar daily dosages of insulin administered via a surgically implanted osmotic pump. Our results demonstrate a significant difference in hepatic enzyme expression when these treatment regimes are compared. In conventionally treated diabetic rats, phosphoenolpyruvate carboxykinase (PEPCK) protein and mRNA levels remained slightly elevated when compared to normal animals, glycogen phosphorylase (GP) protein levels were still slightly decreased, and glycogen synthase (GS) protein and mRNA levels remained at the elevated levels observed in untreated diabetics. In contrast, the protein and mRNA levels of all three enzymes were normalized in the insulin pump-treated animals. These results suggest that intensive insulin therapy improves glycemia directly by normalizing hepatic gene expression while conventional insulin therapy normalizes plasma glucose concentrations indirectly.",
author = "Ken Kramer and Giffin, {Bruce F.} and Fox, {James W.} and Drake, {Richard L.}",
year = "1999",
month = "8",
day = "15",
doi = "10.1006/abbi.1999.1299",
language = "English",
volume = "368",
pages = "291--297",
journal = "Archives of Biochemistry and Biophysics",
issn = "0003-9861",
publisher = "Academic Press Inc.",
number = "2",

}

TY - JOUR

T1 - Insulin replacement therapy in diabetic rats using an osmotic pump normalizes expression of enzymes key to hepatic carbohydrate metabolism

AU - Kramer, Ken

AU - Giffin, Bruce F.

AU - Fox, James W.

AU - Drake, Richard L.

PY - 1999/8/15

Y1 - 1999/8/15

N2 - Intensively treating type I diabetics with continuous subcutaneous insulin infusions or multiple daily insulin injections to normalize mean blood glucose concentrations significantly reduces the onset of secondary diabetic complications when compared to conventionally treated diabetics. Our studies focused on characterizing hepatic enzyme expression in intensively and conventionally treated diabetic rats. Alloxan-induced diabetic rats were conventionally treated with insulin injected twice daily or intensively treated with similar daily dosages of insulin administered via a surgically implanted osmotic pump. Our results demonstrate a significant difference in hepatic enzyme expression when these treatment regimes are compared. In conventionally treated diabetic rats, phosphoenolpyruvate carboxykinase (PEPCK) protein and mRNA levels remained slightly elevated when compared to normal animals, glycogen phosphorylase (GP) protein levels were still slightly decreased, and glycogen synthase (GS) protein and mRNA levels remained at the elevated levels observed in untreated diabetics. In contrast, the protein and mRNA levels of all three enzymes were normalized in the insulin pump-treated animals. These results suggest that intensive insulin therapy improves glycemia directly by normalizing hepatic gene expression while conventional insulin therapy normalizes plasma glucose concentrations indirectly.

AB - Intensively treating type I diabetics with continuous subcutaneous insulin infusions or multiple daily insulin injections to normalize mean blood glucose concentrations significantly reduces the onset of secondary diabetic complications when compared to conventionally treated diabetics. Our studies focused on characterizing hepatic enzyme expression in intensively and conventionally treated diabetic rats. Alloxan-induced diabetic rats were conventionally treated with insulin injected twice daily or intensively treated with similar daily dosages of insulin administered via a surgically implanted osmotic pump. Our results demonstrate a significant difference in hepatic enzyme expression when these treatment regimes are compared. In conventionally treated diabetic rats, phosphoenolpyruvate carboxykinase (PEPCK) protein and mRNA levels remained slightly elevated when compared to normal animals, glycogen phosphorylase (GP) protein levels were still slightly decreased, and glycogen synthase (GS) protein and mRNA levels remained at the elevated levels observed in untreated diabetics. In contrast, the protein and mRNA levels of all three enzymes were normalized in the insulin pump-treated animals. These results suggest that intensive insulin therapy improves glycemia directly by normalizing hepatic gene expression while conventional insulin therapy normalizes plasma glucose concentrations indirectly.

UR - http://www.scopus.com/inward/record.url?scp=0033567147&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033567147&partnerID=8YFLogxK

U2 - 10.1006/abbi.1999.1299

DO - 10.1006/abbi.1999.1299

M3 - Article

VL - 368

SP - 291

EP - 297

JO - Archives of Biochemistry and Biophysics

JF - Archives of Biochemistry and Biophysics

SN - 0003-9861

IS - 2

ER -