Effects of Metformin Treatment on Liver Glucose Metabolism-Related Enzyme Levels in Streptozotocin-Induced Diabetic Rats
- 1Department of Physiotherapy and Rehabilitation, Faculty of Health Sciences, Van Yüzüncü Yıl University, 65080 Van, Turkey
- 2Department of Physiology, Faculty of Medicine, Dicle University, 21000 Diyarbakır, Turkey
- 3Türkoğlu District Health Directorate, Republic of Turkey Ministry of Health, 46800 Kahramanmaraş, Turkey
Abstract
Background: Diabetes mellitus (DM) disrupts hepatic glucose handling and alters pathways involved in glycogen metabolism, glycolysis, the pentose phosphate pathway, and gluconeogenesis. This study examined hepatic glycogen content and glucose metabolism-related enzyme levels at defined stages of streptozotocin (STZ)-induced diabetes and evaluated the effect of metformin at week 8. Methods: Sixty-three adult male Wistar Albino rats were initially allocated to nine groups (n = 7/group): four time-matched control groups (C1–C4), four untreated diabetic groups (D1–D4), and one metformin-treated diabetic group (T). Diabetes was induced with a single intraperitoneal dose of STZ (35 mg/kg). D1/C1, D2/C2, D3/C3, and D4/C4 were evaluated at weeks 1, 3, 6, and 8, respectively; T received metformin (100 mg/kg/day) in drinking water and was evaluated at week 8. One animal each in D3, D4, and T died spontaneously before the scheduled endpoint, leaving 60 animals for final analyses. Hepatic glycogen and glucose metabolism-related enzyme levels were measured by rat-specific sandwich ELISA. Results: Time-matched comparisons showed significant diabetes-associated differences in hepatic glycogen and all measured enzyme levels at weeks 1, 3, 6, and 8. At week 8, metformin shifted glycogen, glycogen synthase (GS), glycogen phosphorylase (GP), lactate dehydrogenase (LDH), pyruvate kinase (PK), hexokinase (HK), glucose-6-phosphatase (G6Pase), glucose-6-phosphate dehydrogenase (G6PD), and fructose-1,6-bisphosphatase (FBP1) toward control values compared with untreated diabetic rats (Holm-adjusted p = 0.0035 for each comparison). However, T remained significantly different from C4 for every hepatic parameter, and final fasting blood glucose did not differ significantly between T and D4. Conclusions: STZ-induced diabetes was associated with marked alterations in hepatic glycogen and glucose metabolism-related enzyme levels. Metformin partially ameliorated these hepatic changes at week 8 despite persistent severe hyperglycemia, but it did not normalize the measured hepatic profile.
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BibTeX
@article{gul2026effects,
title = {{Effects of Metformin Treatment on Liver Glucose Metabolism-Related Enzyme Levels in Streptozotocin-Induced Diabetic Rats}},
author = {Cihan Gül and Mustafa Kelle and Hacer Kayhan Kaya and Bahattin Bulduk and Yılmaz Koçak and Nizamettin Günbatar and İzzet Çeleğen},
journal = {Journal of Clinical Medicine},
year = {2026},
month = oct,
doi = {10.3390/jcm15208108},
url = {https://www.mdpi.com/2077-0383/15/20/8108},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Effects of Metformin Treatment on Liver Glucose Metabolism-Related Enzyme Levels in Streptozotocin-Induced Diabetic Rats
AU - Cihan Gül
AU - Mustafa Kelle
AU - Hacer Kayhan Kaya
AU - Bahattin Bulduk
AU - Yılmaz Koçak
AU - Nizamettin Günbatar
AU - İzzet Çeleğen
PY - 2026
DA - 2026/10/01
JO - Journal of Clinical Medicine
DO - 10.3390/jcm15208108
UR - https://www.mdpi.com/2077-0383/15/20/8108
AB - Background: Diabetes mellitus (DM) disrupts hepatic glucose handling and alters pathways involved in glycogen metabolism, glycolysis, the pentose phosphate pathway, and gluconeogenesis. This study examined hepatic glycogen content and glucose metabolism-related enzyme levels at defined stages of streptozotocin (STZ)-induced diabetes and evaluated the effect of metformin at week 8. Methods: Sixty-three adult male Wistar Albino rats were initially allocated to nine groups (n = 7/group): four time-matched control groups (C1–C4), four untreated diabetic groups (D1–D4), and one metformin-treated diabetic group (T). Diabetes was induced with a single intraperitoneal dose of STZ (35 mg/kg). D1/C1, D2/C2, D3/C3, and D4/C4 were evaluated at weeks 1, 3, 6, and 8, respectively; T received metformin (100 mg/kg/day) in drinking water and was evaluated at week 8. One animal each in D3, D4, and T died spontaneously before the scheduled endpoint, leaving 60 animals for final analyses. Hepatic glycogen and glucose metabolism-related enzyme levels were measured by rat-specific sandwich ELISA. Results: Time-matched comparisons showed significant diabetes-associated differences in hepatic glycogen and all measured enzyme levels at weeks 1, 3, 6, and 8. At week 8, metformin shifted glycogen, glycogen synthase (GS), glycogen phosphorylase (GP), lactate dehydrogenase (LDH), pyruvate kinase (PK), hexokinase (HK), glucose-6-phosphatase (G6Pase), glucose-6-phosphate dehydrogenase (G6PD), and fructose-1,6-bisphosphatase (FBP1) toward control values compared with untreated diabetic rats (Holm-adjusted p = 0.0035 for each comparison). However, T remained significantly different from C4 for every hepatic parameter, and final fasting blood glucose did not differ significantly between T and D4. Conclusions: STZ-induced diabetes was associated with marked alterations in hepatic glycogen and glucose metabolism-related enzyme levels. Metformin partially ameliorated these hepatic changes at week 8 despite persistent severe hyperglycemia, but it did not normalize the measured hepatic profile.
SN - 2077-0383
ER -