Modulation of GPC-4 and GPLD1 serum levels by improving glycemic indices in type 2 diabetes: Resistance training and hawthorn extract intervention

doi:10.1016/j.heliyon.2023.e15537

. 2023 Apr 15;9(4):e15537.

doi: 10.1016/j.heliyon.2023.e15537. eCollection 2023 Apr.

Modulation of GPC-4 and GPLD1 serum levels by improving glycemic indices in type 2 diabetes: Resistance training and hawthorn extract intervention

Ali Heidarianpour¹, Maryam Keshvari¹, Siamak Shahidi^{2

3}, Mohammad Zarei^{2

3}

Affiliations

¹ Bu- Ali Sina University, Faculty of Sport Sciences, Hamedan, Iran.
² Department of Physiology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.
³ Neurophysiology Research Center, Hamadan University of Medical Sciences, Hamadan, Iran.

PMID: 37151681
PMCID: PMC10161711
DOI: 10.1016/j.heliyon.2023.e15537

Modulation of GPC-4 and GPLD1 serum levels by improving glycemic indices in type 2 diabetes: Resistance training and hawthorn extract intervention

Ali Heidarianpour et al. Heliyon. 2023.

. 2023 Apr 15;9(4):e15537.

doi: 10.1016/j.heliyon.2023.e15537. eCollection 2023 Apr.

Authors

Ali Heidarianpour¹, Maryam Keshvari¹, Siamak Shahidi^{2

3}, Mohammad Zarei^{2

3}

Affiliations

¹ Bu- Ali Sina University, Faculty of Sport Sciences, Hamedan, Iran.
² Department of Physiology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.
³ Neurophysiology Research Center, Hamadan University of Medical Sciences, Hamadan, Iran.

PMID: 37151681
PMCID: PMC10161711
DOI: 10.1016/j.heliyon.2023.e15537

Abstract

Aims: This study was designed to investigate the effects of resistance training (RT) and hawthorn extract (Ha) on Glypican-4 (GPC-4) and Insulin-regulated glycosylphosphatidylinositol-specific phospholipase D (GPLD1) serum levels in T2DM and to examine the relationship of these variables with glycemic indexes.

Method: 40 male Wistar rats were divided into five equal groups: Healthy Control (H-C), Diabetes Control (D-C), Diabetes Resistance training (D-RT), Diabetes Hawthorn (D-Ha), and Diabetes Resistance training Hawthorn (D-RT-Ha). T2DM was induced with a 4-week high-fat diet (HFD) and one dose of STZ intraperitoneal injection (35 mg/kg). 1-week after the injection, RT (with a range of 50%-100%1RM/3 day/week) and gavage of Ha extract (100 mg/kg/day) was performed for 12 weeks.

Results: The glycemic indices improvement (reducing blood glucose and increasing serum insulin level) caused by RT and/or Ha increased GPC-4 and decreased GPLD1 in the T2DM rats, but these positive changes were more effective in the combination of RT + Ha. A strong correlation was also observed between GPC-4 and GPLD1 with blood glucose and insulin.

Conclusion: The increase in serum GPC-4 levels was probably due to the direct effect of RT + Ha, and the improvement of glycemic indexes after RT and Ha. The double effect of RT + Ha can be a regulatory mechanism for GPC-4 and its related factors in controlling T2DM complications.

Keywords: Diabetes; Exercise training; GPC-4; GPLD1; Insulin; Medicinal plants.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

**Fig. 1**
Outline of the implementation of the study protocol.

**Fig. 2**
The compositions of *hawthorn* extract by HPLC. The calibration range of each compound was as follows: catechin (0.16–36.6 μg), chlorogenic acid (0.75–9.80 μg), epigallocatechin gallate (0.21–32.76 μg), rutin (0.62–9.70 μg), vitexin (0.37–5.95 μg), isocercetin (0.66–16.40 μg), quercetin (0.11–11.40 μg), methoxykaempferol-hexoside (0.87–5.74 μg), apigenin (0.18–8.0 μg), gallocatechin gallate (0.14–4.87 μg), vitexin-2″-O-rhamnoside (0.84–19.45 μg), isoquercitrin (0.54–6.98 μg), hyperoside (0.43–8.23 μg), and resveratrol (0.85–25.8 μg).

**Fig. 3**
RT + Ha improved glycemic index and increased serum GPC-4 levels. Changes of FBG (I), FIns (II), HOMA-IR (III), HOMA-IS (IV), GPC-4 (V), and GPLD1 (VI) in diabetic rats following 12 weeks of resistance training and *hawthorn* extract treatment. * Significantly different (P < 0.05), ** significantly different (P < 0.01), *** significantly different (P < 0.001). (ANOVA and subsequent Tukey's HSD, P < 0.05).

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References

1. Theerthagiri P., Ruby A.U., Vidya J. Diagnosis and classification of the diabetes using machine learning algorithms. SN Comput. Sci. 2022;4(1):72.
1. Gheitasi I., Savari F., Akbari G., Mohammadi J., Fallahzadeh A.R., Sadeghi H. Molecular mechanisms of hawthorn extracts in multiple organs disorders in underlying of diabetes: a review. Int. J. Endocrinol. 2022;2022 - PMC - PubMed
1. Abdolmaleki F., Heidarianpour A. Endurance exercise training restores diabetes-induced alteration in circulating Glycosylphosphatidylinositol-specific phospholipase D levels in rats. Diabetol. Metab. Syndrome. 2020;12(1):1–8. - PMC - PubMed
1. Ussar S., Bezy O., Blüher M., Kahn C.R. Glypican-4 enhances insulin signaling via interaction with the insulin receptor and serves as a novel adipokine. Diabetes. 2012;61(9):2289–2298. - PMC - PubMed
1. Zhu H.J., Pan H., Cui Y., Wang X.Q., Wang L.J., Li N.S., Yang H.B., Gong F.Y. The changes of serum glypican4 in obese patients with different glucose metabolism status. J. Clin. Endocrinol. Metab. 2014;99(12):E2697–E2701. - PubMed

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[1] Theerthagiri P., Ruby A.U., Vidya J. Diagnosis and classification of the diabetes using machine learning algorithms. SN Comput. Sci. 2022;4(1):72.

[2] Theerthagiri P., Ruby A.U., Vidya J. Diagnosis and classification of the diabetes using machine learning algorithms. SN Comput. Sci. 2022;4(1):72.

[3] Gheitasi I., Savari F., Akbari G., Mohammadi J., Fallahzadeh A.R., Sadeghi H. Molecular mechanisms of hawthorn extracts in multiple organs disorders in underlying of diabetes: a review. Int. J. Endocrinol. 2022;2022 - PMC - PubMed

[4] Gheitasi I., Savari F., Akbari G., Mohammadi J., Fallahzadeh A.R., Sadeghi H. Molecular mechanisms of hawthorn extracts in multiple organs disorders in underlying of diabetes: a review. Int. J. Endocrinol. 2022;2022 - PMC - PubMed

[5] Abdolmaleki F., Heidarianpour A. Endurance exercise training restores diabetes-induced alteration in circulating Glycosylphosphatidylinositol-specific phospholipase D levels in rats. Diabetol. Metab. Syndrome. 2020;12(1):1–8. - PMC - PubMed

[6] Abdolmaleki F., Heidarianpour A. Endurance exercise training restores diabetes-induced alteration in circulating Glycosylphosphatidylinositol-specific phospholipase D levels in rats. Diabetol. Metab. Syndrome. 2020;12(1):1–8. - PMC - PubMed

[7] Ussar S., Bezy O., Blüher M., Kahn C.R. Glypican-4 enhances insulin signaling via interaction with the insulin receptor and serves as a novel adipokine. Diabetes. 2012;61(9):2289–2298. - PMC - PubMed

[8] Ussar S., Bezy O., Blüher M., Kahn C.R. Glypican-4 enhances insulin signaling via interaction with the insulin receptor and serves as a novel adipokine. Diabetes. 2012;61(9):2289–2298. - PMC - PubMed

[9] Zhu H.J., Pan H., Cui Y., Wang X.Q., Wang L.J., Li N.S., Yang H.B., Gong F.Y. The changes of serum glypican4 in obese patients with different glucose metabolism status. J. Clin. Endocrinol. Metab. 2014;99(12):E2697–E2701. - PubMed

[10] Zhu H.J., Pan H., Cui Y., Wang X.Q., Wang L.J., Li N.S., Yang H.B., Gong F.Y. The changes of serum glypican4 in obese patients with different glucose metabolism status. J. Clin. Endocrinol. Metab. 2014;99(12):E2697–E2701. - PubMed

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Modulation of GPC-4 and GPLD1 serum levels by improving glycemic indices in type 2 diabetes: Resistance training and hawthorn extract intervention

Affiliations

Modulation of GPC-4 and GPLD1 serum levels by improving glycemic indices in type 2 diabetes: Resistance training and hawthorn extract intervention

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Affiliations

Abstract

Conflict of interest statement

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