See the published version of this preprint at Stem Cell Research & Therapy.
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Research
Shuang-chun Liu
Municipal Hospital Affiliated Medical School of Taizhou University
Corresponding Author
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Background: Globally, 1 in 11 adults have diabetes mellitus and 90% of the cases are type 2 diabetes mellitus. Insulin resistance is a central defect in type 2 diabetes mellitus, and although multiple drugs have been developed to ameliorate insulin resistance, the limitations and accompanying side effects cannot be ignored. Thus more effective methods are required to improve insulin resistance.
Methods: In the current study, db/m and db/dbmice were injected with human umbilical cord-derived mesenchymal stem cells (HUC-MSCs) via tail vein injection, intraperitoneal injection and skeletal muscle injection. Body weight, fasting blood glucose and the survival rates were monitored. Furthermore, the anti-insulin resistance effects and potential mechanisms of transplanted HUC-MSCs were investigated in db/db mice in vivo.
Results: The results showed that HUC-MSC transplantation by skeletal muscle injection was safer compared with tail vein injection and intraperitoneal injection, and the survival rate reached 100% in the skeletal muscle injection transplanted mice. HUC-MSCs can stabilize localization and differentiation in skeletal muscle tissue and significantly ameliorate insulin resistance. Potential regulatory mechanisms are associated with downregulation of inflammation; regulating the balance between PI3K/Akt and ERK/MAPK signaling pathway via PTEN, but was not associated with the IGF-1/IGF-1R signaling pathway.
Conclusions: These results suggest HUC-MSC transplantation may be a novel therapeutic direction to prevent insulin resistance and increase insulin sensitivity, and skeletal muscle injection was the safest and most effective way.
Keywords
HUC-MSCs, insulin resistant, PTEN, crosstalk, PI3K/Akt, Erk/MAPK, db/db mice
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CURRENT STATUS: Published
View the published article at Stem Cell Research & Therapy.
Version 4
Posted 30 Jul, 2020
No community comments so far
Editor assigned
On 24 Jul, 2020
Editorial decision: Accept
On 24 Jul, 2020
Submission checks complete
On 23 Jul, 2020
Editor invited
On 23 Jul, 2020
No comments provided
Editorial decision: Major Revision
On 14 Jul, 2020
Review #1 received
Received 19 Jun, 2020
Review #3 received
Received 10 Jun, 2020
Review #2 received
Received 10 Jun, 2020
Reviewer #3 agreed
On 06 Jun, 2020
Reviewers invited
Invitations sent on 04 Jun, 2020
Reviewer #1 agreed
On 04 Jun, 2020
Reviewer #2 agreed
On 04 Jun, 2020
Editor assigned
On 26 May, 2020
Submission checks complete
On 25 May, 2020
Editor invited
On 25 May, 2020
No comments provided
Editorial decision: Minor Revision
On 18 May, 2020
Review #2 received
Received 15 May, 2020
Review #3 received
Received 15 May, 2020
Review #1 received
Received 13 May, 2020
Reviewer #4 agreed
On 07 May, 2020
Reviewer #3 agreed
On 07 May, 2020
Reviewer #2 agreed
On 05 May, 2020
Reviewers invited
Invitations sent on 28 Apr, 2020
Reviewer #1 agreed
On 28 Apr, 2020
Editor assigned
On 20 Apr, 2020
Submission checks complete
On 19 Apr, 2020
Editor invited
On 19 Apr, 2020
No comments provided
Editorial decision: Major Revision
On 03 Apr, 2020
Review #2 received
Received 09 Mar, 2020
Reviewer #1 agreed
On 09 Mar, 2020
Reviewer #2 agreed
On 09 Mar, 2020
Review #1 received
Received 09 Mar, 2020
Reviewers invited
Invitations sent on 05 Mar, 2020
Editor assigned
On 24 Feb, 2020
Editor invited
On 23 Feb, 2020
Submission checks complete
On 21 Feb, 2020
First submitted
On 18 Feb, 2020
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See the published version of this preprint at Stem Cell Research & Therapy.
This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research
Shuang-chun Liu
Municipal Hospital Affiliated Medical School of Taizhou University
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
View the published article at Stem Cell Research & Therapy.
Version 4
Posted 30 Jul, 2020
No community comments so far
Editor assigned
On 24 Jul, 2020
Editorial decision: Accept
On 24 Jul, 2020
Submission checks complete
On 23 Jul, 2020
Editor invited
On 23 Jul, 2020
No comments provided
Editorial decision: Major Revision
On 14 Jul, 2020
Review #1 received
Received 19 Jun, 2020
Review #3 received
Received 10 Jun, 2020
Review #2 received
Received 10 Jun, 2020
Reviewer #3 agreed
On 06 Jun, 2020
Reviewers invited
Invitations sent on 04 Jun, 2020
Reviewer #1 agreed
On 04 Jun, 2020
Reviewer #2 agreed
On 04 Jun, 2020
Editor assigned
On 26 May, 2020
Submission checks complete
On 25 May, 2020
Editor invited
On 25 May, 2020
No comments provided
Editorial decision: Minor Revision
On 18 May, 2020
Review #2 received
Received 15 May, 2020
Review #3 received
Received 15 May, 2020
Review #1 received
Received 13 May, 2020
Reviewer #4 agreed
On 07 May, 2020
Reviewer #3 agreed
On 07 May, 2020
Reviewer #2 agreed
On 05 May, 2020
Reviewers invited
Invitations sent on 28 Apr, 2020
Reviewer #1 agreed
On 28 Apr, 2020
Editor assigned
On 20 Apr, 2020
Submission checks complete
On 19 Apr, 2020
Editor invited
On 19 Apr, 2020
No comments provided
Editorial decision: Major Revision
On 03 Apr, 2020
Review #2 received
Received 09 Mar, 2020
Reviewer #1 agreed
On 09 Mar, 2020
Reviewer #2 agreed
On 09 Mar, 2020
Review #1 received
Received 09 Mar, 2020
Reviewers invited
Invitations sent on 05 Mar, 2020
Editor assigned
On 24 Feb, 2020
Editor invited
On 23 Feb, 2020
Submission checks complete
On 21 Feb, 2020
First submitted
On 18 Feb, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published article at Stem Cell Research & Therapy.
Background: Globally, 1 in 11 adults have diabetes mellitus and 90% of the cases are type 2 diabetes mellitus. Insulin resistance is a central defect in type 2 diabetes mellitus, and although multiple drugs have been developed to ameliorate insulin resistance, the limitations and accompanying side effects cannot be ignored. Thus more effective methods are required to improve insulin resistance.
Methods: In the current study, db/m and db/dbmice were injected with human umbilical cord-derived mesenchymal stem cells (HUC-MSCs) via tail vein injection, intraperitoneal injection and skeletal muscle injection. Body weight, fasting blood glucose and the survival rates were monitored. Furthermore, the anti-insulin resistance effects and potential mechanisms of transplanted HUC-MSCs were investigated in db/db mice in vivo.
Results: The results showed that HUC-MSC transplantation by skeletal muscle injection was safer compared with tail vein injection and intraperitoneal injection, and the survival rate reached 100% in the skeletal muscle injection transplanted mice. HUC-MSCs can stabilize localization and differentiation in skeletal muscle tissue and significantly ameliorate insulin resistance. Potential regulatory mechanisms are associated with downregulation of inflammation; regulating the balance between PI3K/Akt and ERK/MAPK signaling pathway via PTEN, but was not associated with the IGF-1/IGF-1R signaling pathway.
Conclusions: These results suggest HUC-MSC transplantation may be a novel therapeutic direction to prevent insulin resistance and increase insulin sensitivity, and skeletal muscle injection was the safest and most effective way.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
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