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Hypoxic mesenchymal stem cell-derived secretome and alkaline water synergistically reduce apoptosis and insulin resistance in type 2 diabetes mellitus rat model

Universa Medicina · Vol. 44 No. 3 (2025) · pp. 310–317

DOI
10.18051/UnivMed.2025.v44.310-317
ISSN
2407-2230, 1907-3062
Published
2025-11-11
Publisher
Faculty of Medicine, Universitas Trisakti
Language
eng
License
creativecommons.org/licenses/by-nc-sa/4.0

Abstract

BACKGROUNDType 2 Diabetes Mellitus (T2DM) is characterized by chronic inflammation and insulin resistance. These factors contribute to pancreatic β-cell apoptosis, reducing insulin production and impairing glucose homeostasis. This study aims to evaluate the protective effects of hypoxic mesenchymal stem cell-derived secretome (HMSCS) and alkaline water on inflammation, apoptosis, and insulin resistance in a T2DM rat model. METHODSAn experimental study was conducted involving 24 male Wistar T2DM model rats (aged 6-8 weeks, 200-250g). They were randomized into four groups: T2DM rats only as negative control (K-), T2DM rats with metformin as positive control (K+), HMSCS treatment (P1), and HMSCS plus alkaline water group (P2). Caspase-3 expression was measured to assess apoptosis levels using RT-PCR, while homeostatic model assessment for insulin resistance (HOMA-IR) was measured using ELISA. One way ANOVA followed by a post hoc LSD test were used to analyse the data. RESULTSThe P1 group (3.03 ± 1.26 a.u) and P2 group (2.93 ± 0.52 a.u.) had significantly lower caspase-3 expression compared to K- group (6.66 ± 2.76 a.u.) (p 0.05). Additionally, P2 group (6.76 ± 0.96) had a significantly lower HOMA-IR than K- group (18.92 ± 2.63) and K+ group (10.85 ± 1.39) (p<0.05), and similarly the P1 (7.71 ± 0.53) group also showed significant difference from K- and K+ groups (p<0.05). CONCLUSIONHigher doses of HMSCS and alkaline water are associated with reduced pancreatic β-cell apoptosis and improved insulin sensitivity, highlighting its potential as a novel therapeutic approach for T2DM.

Keywords

Collaboration network of the authors

40 authors · 106 co-authorship links · 2 across different organisations · showing the 40 most connected

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  • University of Brawijaya
  • Universitas Islam Indragiri
  • Padjadjaran University
  • Affiliation unknown
  • Different organisations
  • Same organisation
  • Affiliation unknown
  • Thicker line = more joint articles · bigger circle = more articles
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Co-authorOrganisationJoint articles
Titiek SumarawatiAffiliation unknown6
Nurul HidayahAffiliation unknown5
Nur Dina AmalinaAffiliation unknown3
Iffan AlifAffiliation unknown3
Sri Priyantini MulyaniAffiliation unknown3
Sugeng IbrahimAffiliation unknown3
Chodidjah ChodidjahAffiliation unknown3
Hurriyatul FitriyahUniversity of Brawijaya2
Agung Setia BudiUniversity of Brawijaya2
Rizal MaulanaUniversity of Brawijaya2
Sabriansyah Rizqika AkbarUniversity of Brawijaya2
Chodijah ChodijahAffiliation unknown2
Adi Muradi MuharAffiliation unknown2
Bayu Tirta DirjaAffiliation unknown2
Salma Yasmine AzzaharaAffiliation unknown2
Setyo TrisnadiAffiliation unknown2
Muhammad Rheza CaesardiUniversity of Brawijaya1
Jeffry Atur FirdausUniversity of Brawijaya1
Agung SetiabudiUniversitas Islam Indragiri1
Fahmi ErzaUniversity of Brawijaya1
Rakhmadhany PrimanandaUniversity of Brawijaya1
Naufal Mohamad GhifaryAffiliation unknown1
Cleveria JessikaAffiliation unknown1
Carolina Kiwik RahardjaAffiliation unknown1
Alisia Martha DewiAffiliation unknown1
Setyo TrisnasiAffiliation unknown1
Hadi SarosaAffiliation unknown1
Yoshi PuspitasariAffiliation unknown1
Y. Titik HaryatiAffiliation unknown1
Siti Jaro'ahAffiliation unknown1
Navthan LuftaAffiliation unknown1
Adiwignya Nugraha Widi HaritaAffiliation unknown1
Lakkana SuwannoiAffiliation unknown1
Preecha MontakantikulAffiliation unknown1
Busba ChindavijakAffiliation unknown1
Mas Rizky A. A. SyamsunarnoPadjadjaran University1
Tarrayuana Rhamadia HasannuriAffiliation unknown1

Affiliations come from OpenAlex; journal OAI-PMH metadata carries none. Authors without an OpenAlex ID are matched by name, which can merge or split people.

Metadata source: OAI-PMH (metadata jurnal) https://univmed.org/ejurnal/index.php/medicina/oai, first harvested 10 Nov 2026, last seen 10 Nov 2026.
Original metadata (oai_dc) 
<oai_dc:dc xmlns="http://www.openarchives.org/OAI/2.0/" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:oai_dc="http://www.openarchives.org/OAI/2.0/oai_dc/" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xsi:schemaLocation="http://www.openarchives.org/OAI/2.0/oai_dc/  http://www.openarchives.org/OAI/2.0/oai_dc.xsd">
	<dc:title xml:lang="en">Hypoxic mesenchymal stem cell-derived secretome and alkaline water synergistically reduce apoptosis and insulin resistance in type 2 diabetes mellitus rat model</dc:title>
	<dc:creator xml:lang="en">Mawarini, Melisa Septi</dc:creator>
	<dc:creator xml:lang="en">Setiawan, Eko</dc:creator>
	<dc:creator xml:lang="en">Putra, Agung</dc:creator>
	<dc:subject xml:lang="en">Caspase-3</dc:subject>
	<dc:subject xml:lang="en">HOMA-IR</dc:subject>
	<dc:subject xml:lang="en">inflammation</dc:subject>
	<dc:subject xml:lang="en">insulin resistance</dc:subject>
	<dc:subject xml:lang="en">HMSCS</dc:subject>
	<dc:subject xml:lang="en">T2DM</dc:subject>
	<dc:subject xml:lang="en">rats</dc:subject>
	<dc:description xml:lang="en">BACKGROUNDType 2 Diabetes Mellitus (T2DM) is characterized by chronic inflammation and insulin resistance. These factors contribute to pancreatic β-cell apoptosis, reducing insulin production and impairing glucose homeostasis. This study aims to evaluate the protective effects of hypoxic mesenchymal stem cell-derived secretome (HMSCS) and alkaline water on inflammation, apoptosis, and insulin resistance in a T2DM rat model.
METHODSAn experimental study was conducted involving 24 male Wistar T2DM model rats (aged 6-8 weeks, 200-250g). They were randomized into four groups: T2DM rats only as negative control (K-), T2DM rats with metformin as positive control (K+), HMSCS treatment (P1), and HMSCS plus alkaline water group (P2). Caspase-3 expression was measured to assess apoptosis levels using RT-PCR, while homeostatic model assessment for insulin resistance (HOMA-IR) was measured using ELISA. One way ANOVA followed by a post hoc LSD test were used to analyse the data.
RESULTSThe P1 group (3.03 ± 1.26 a.u) and P2 group (2.93 ± 0.52 a.u.) had significantly lower caspase-3 expression compared to K- group (6.66 ± 2.76 a.u.) (p&amp;lt;0.05), but were not significantly different from K+ group (3.83 ± 1.61 a.u.) (p&amp;gt;0.05). Additionally, P2 group (6.76 ± 0.96) had a significantly lower HOMA-IR than K- group (18.92 ± 2.63) and K+ group (10.85 ± 1.39) (p&amp;lt;0.05), and similarly the P1 (7.71 ± 0.53) group also showed significant difference from K- and K+ groups (p&amp;lt;0.05).
CONCLUSIONHigher doses of HMSCS and alkaline water are associated with reduced pancreatic β-cell apoptosis and improved insulin sensitivity, highlighting its potential as a novel therapeutic approach for T2DM.</dc:description>
	<dc:publisher xml:lang="en">Faculty of Medicine, Universitas Trisakti</dc:publisher>
	<dc:date>2025-11-11</dc:date>
	<dc:type>info:eu-repo/semantics/article</dc:type>
	<dc:type>info:eu-repo/semantics/publishedVersion</dc:type>
	<dc:format>application/pdf</dc:format>
	<dc:identifier>https://univmed.org/ejurnal/index.php/medicina/article/view/1772</dc:identifier>
	<dc:identifier>10.18051/UnivMed.2025.v44.310-317</dc:identifier>
	<dc:source xml:lang="en">Universa Medicina; Vol. 44 No. 3 (2025); 310-317</dc:source>
	<dc:source>2407-2230</dc:source>
	<dc:source>1907-3062</dc:source>
	<dc:source>10.18051/UnivMed.2025.v44.i3</dc:source>
	<dc:language>eng</dc:language>
	<dc:relation>https://univmed.org/ejurnal/index.php/medicina/article/view/1772/842</dc:relation>
	<dc:rights xml:lang="en">Copyright (c) 2025 Melissa Septi Mawarini, Eko Setiawan, Agung Putra</dc:rights>
	<dc:rights xml:lang="en">https://creativecommons.org/licenses/by-nc-sa/4.0</dc:rights>
</oai_dc:dc>