TY - JOUR

T1 - Actovegin improves skeletal muscle mitochondrial respiration and functional aerobic capacity in a type 1 diabetic male murine model

AU - Kosik, Brandon

AU - Larsen, Steen

AU - Bergdahl, Andreas

N1 - Publisher Copyright: © 2023 The Author(s).

PY - 2024

Y1 - 2024

N2 - Insulin deficiency in type 1 diabetes (T1D) leads to an impairment of glucose metabolism and mitochondrial function. Ac-tovegin is a hemodialysate of calf blood, which has been shown to enhance glucose uptake and cell metabolism in healthy human skeletal muscle. The objectives of this study were to determine the effects of Actovegin on skeletal muscle mitochon-drial respiration and functional aerobic capacity in a T1D mouse model. Effects on the expression of mitochondrial proteins, body mass, and food and water consumption were also investigated. Streptozotocin-induced T1D male C57B1/6 mice (aged 3–4 months) were randomized to an Actovegin group and a control group. Every third day, the Actovegin and control groups were injected intraperitoneally with (0.1 mL) Actovegin and (0.1 mL) physiological salt solution, respectively. Oxidative phos-phorylation (OXPHOS) capacity of the vastus lateralis muscle was measured by high resolution respirometry in addition to the expression levels of the mitochondrial complexes as well as voltage-dependent anion channel. Functional aerobic capacity was measured using a rodent treadmill protocol. Body mass and food and water consumption were also measured. After 13 days, in comparison to the control group, the Actovegin group demonstrated a significantly higher skeletal muscle mitochon-drial respiratory capacity in an ADP-restricted and ADP-stimulated environment. The Actovegin group displayed a significantly lesser decline in functional aerobic capacity and baseline body mass after 13 days. There were no significant differences in food or water consumption between groups. Actovegin could act as an effective agent for facilitating glucose metabolism and im-proving OXPHOS capacity and functional aerobic capacity in T1D. Further investigation is warranted to establish Actovegin’s potential as an alternative therapeutic drug for T1D.

AB - Insulin deficiency in type 1 diabetes (T1D) leads to an impairment of glucose metabolism and mitochondrial function. Ac-tovegin is a hemodialysate of calf blood, which has been shown to enhance glucose uptake and cell metabolism in healthy human skeletal muscle. The objectives of this study were to determine the effects of Actovegin on skeletal muscle mitochon-drial respiration and functional aerobic capacity in a T1D mouse model. Effects on the expression of mitochondrial proteins, body mass, and food and water consumption were also investigated. Streptozotocin-induced T1D male C57B1/6 mice (aged 3–4 months) were randomized to an Actovegin group and a control group. Every third day, the Actovegin and control groups were injected intraperitoneally with (0.1 mL) Actovegin and (0.1 mL) physiological salt solution, respectively. Oxidative phos-phorylation (OXPHOS) capacity of the vastus lateralis muscle was measured by high resolution respirometry in addition to the expression levels of the mitochondrial complexes as well as voltage-dependent anion channel. Functional aerobic capacity was measured using a rodent treadmill protocol. Body mass and food and water consumption were also measured. After 13 days, in comparison to the control group, the Actovegin group demonstrated a significantly higher skeletal muscle mitochon-drial respiratory capacity in an ADP-restricted and ADP-stimulated environment. The Actovegin group displayed a significantly lesser decline in functional aerobic capacity and baseline body mass after 13 days. There were no significant differences in food or water consumption between groups. Actovegin could act as an effective agent for facilitating glucose metabolism and im-proving OXPHOS capacity and functional aerobic capacity in T1D. Further investigation is warranted to establish Actovegin’s potential as an alternative therapeutic drug for T1D.

KW - Actovegin

KW - aerobic capacity

KW - diabetes

KW - exercise

KW - mitochondrial respiration

U2 - 10.1139/apnm-2023-0004

DO - 10.1139/apnm-2023-0004

M3 - Journal article

C2 - 37913525

AN - SCOPUS:85184149818

VL - 49

SP - 265

EP - 272

JO - Applied Physiology, Nutrition and Metabolism

JF - Applied Physiology, Nutrition and Metabolism

SN - 1715-5312

IS - 2

ER -