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Incretins include glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which stimulate insulin secretion post-meals. In type 2 diabetes, GIP's efficacy is reduced, making GLP-1 a viable drug target. GIP originates from preproGIP.
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Dipeptidyl peptidase 4 (DPP-4) is a serine protease widely distributed in the body. It's involved in the inactivation of GLP-1 and GIP hormones, which are crucial for insulin regulation. DPP-4 inhibitors, such as sitagliptin (Januvia), saxagliptin (Onglyza), linagliptin (Tradjenta), alogliptin (Nesina), and vildagliptin (Galvus), help increase the proportion of active GLP-1, enhancing insulin secretion. These inhibitors work by competitively binding to DPP-4. This binding causes a...
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Diabetes mellitus is a chronic metabolic disorder characterized by high blood glucose levels due to inadequate insulin production, insulin resistance, or both. The condition affects millions worldwide and can significantly impact their health and quality of life.
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Injectable skeletal muscle constructs overexpressing GLUT4 for type 2 diabetes intervention.

Hagit Shoyhet1, Yifat Herman Bachinsky2, Margarita Bekerman2

  • 1Faculty of Biomedical Engineering, Technion, Israel; The Norman Seiden Multidisciplinary Graduate program in Nanotechnology & Nanoscience, Technion, Israel.

Acta Biomaterialia
|March 17, 2025
PubMed
Summary
This summary is machine-generated.

Engineered injectable muscle tissue using a shape-memory scaffold offers a minimally invasive treatment for Type 2 diabetes. This GLUT4-overexpressing construct improves glucose homeostasis and integrates with native muscle.

Keywords:
Injectable scaffoldShape-memory scaffoldSkeletal muscleTissue engineeringType II diabetes

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Area of Science:

  • Regenerative Medicine
  • Biomaterials Science
  • Metabolic Disease Research

Background:

  • Skeletal muscle tissue engineering faces challenges with large constructs and invasive implantation.
  • Injectable scaffolds are emerging, but skeletal muscle fabrication is complex due to myotube size and mechanical needs.
  • Type 2 diabetes is marked by reduced GLUT4 expression and translocation in skeletal muscle, impairing glucose regulation.

Purpose of the Study:

  • To develop an injectable, shape-memory collagen scaffold for skeletal muscle tissue engineering.
  • To create GLUT4-overexpressing muscle constructs for potential Type 2 diabetes treatment.
  • To demonstrate minimally invasive delivery and in vivo efficacy of engineered muscle tissue.

Main Methods:

  • Fabrication of a collagen-based shape-memory scaffold.
  • Development of injectable, GLUT4-overexpressing skeletal muscle constructs.
  • Intramuscular delivery via syringe needle and in vivo assessment in a Type 2 diabetes mouse model.

Main Results:

  • The injectable scaffold maintained shape post-injection and supported muscle growth and differentiation in vitro.
  • Engineered muscle constructs integrated successfully with native muscle tissue.
  • GLUT4-overexpressing constructs improved glucose homeostasis in diabetic mice, retaining viability and shape-memory properties.

Conclusions:

  • Minimally invasive delivery of engineered skeletal muscle tissue is feasible using shape-memory scaffolds.
  • Injectable GLUT4-overexpressing muscle constructs show potential for treating Type 2 diabetes by improving glucose regulation.
  • This approach advances regenerative medicine for chronic metabolic disorders requiring enhanced muscle function.