New Treatment for Type 2 Diabetes Mellitus Using a Novel Bipyrazole Compound.

Alqudah, A; Qnais, EY; Wedyan, MA; Altaber, S; Abudalo, R; Gammoh, O; Alkhateeb, H; Bataineh, S; Athamneh, RY; Oqal, M; Abu-Safieh, K; McClements, L

New Treatment for Type 2 Diabetes Mellitus Using a Novel Bipyrazole Compound.

Alqudah, A Qnais, EY Wedyan, MA Altaber, S Abudalo, R Gammoh, O Alkhateeb, H Bataineh, S Athamneh, RY Oqal, M Abu-Safieh, K McClements, L

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Publisher:: MDPI
Publication Type:: Journal Article
Citation:: Cells, 2023, 12, (2), pp. 267
Issue Date:: 2023-01-09

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Field	Value	Language
dc.contributor.author	Alqudah, A
dc.contributor.author	Qnais, EY
dc.contributor.author	Wedyan, MA
dc.contributor.author	Altaber, S
dc.contributor.author	Abudalo, R
dc.contributor.author	Gammoh, O
dc.contributor.author	Alkhateeb, H
dc.contributor.author	Bataineh, S
dc.contributor.author	Athamneh, RY
dc.contributor.author	Oqal, M
dc.contributor.author	Abu-Safieh, K
dc.contributor.author	McClements, L https://orcid.org/0000-0002-4911-1014
dc.date.accessioned	2024-02-12T06:07:48Z
dc.date.available	2023-01-05
dc.date.available	2024-02-12T06:07:48Z
dc.date.issued	2023-01-09
dc.identifier.citation	Cells, 2023, 12, (2), pp. 267
dc.identifier.issn	2073-4409
dc.identifier.issn	2073-4409
dc.identifier.uri	http://hdl.handle.net/10453/175586
dc.description.abstract	2',3,3,5'-Tetramethyl-4'-nitro-2'H-1,3'-bipyrazole (TMNB) is a novel bipyrazole compound with unknown therapeutic potential in diabetes mellitus. This study aims to investigate the anti-diabetic effects of TMNB in a high-fat diet and streptozotocin-(HFD/STZ)-induced rat model of type 2 diabetes mellitus (T2D). Rats were fed HFD, followed by a single low dose of STZ (40 mg/kg). HFD/STZ diabetic rats were treated orally with TMNB (10 mg/kg) or (200 mg/kg) metformin for 10 days before terminating the experiment and collecting plasma, soleus muscle, adipose tissue, and liver for further downstream analysis. TMNB reduced the elevated levels of serum glucose in diabetic rats compared to the vehicle control group (p < 0.001). TMNB abrogated the increase in serum insulin in the treated diabetic group compared to the vehicle control rats (p < 0.001). The homeostasis model assessment of insulin resistance (HOMA-IR) was decreased in the diabetic rats treated with TMNB compared to the vehicle controls. The skeletal muscle and adipose tissue protein contents of GLUT4 and AMPK were upregulated following treatment with TMNB (p < 0.001, < 0.01, respectively). TMNB was able to upregulate GLUT2 and AMPK protein expression in liver (p < 0.001, < 0.001, respectively). LDL, triglyceride, and cholesterol were reduced in diabetic rats treated with TMNB compared to the vehicle controls (p < 0.001, 0.01, respectively). TMNB reduced MDA and IL-6 levels (p < 0.001), and increased GSH level (p < 0.05) in diabetic rats compared to the vehicle controls. Conclusion: TMNB ameliorates insulin resistance, oxidative stress, and inflammation in a T2D model. TMNB could represent a promising therapeutic agent to treat T2D.
dc.format	Electronic
dc.language	eng
dc.publisher	MDPI
dc.relation.ispartof	Cells
dc.relation.isbasedon	10.3390/cells12020267
dc.rights	info:eu-repo/semantics/openAccess
dc.subject.classification	31 Biological sciences
dc.subject.classification	32 Biomedical and clinical sciences
dc.subject.mesh	Rats
dc.subject.mesh	Animals
dc.subject.mesh	Diabetes Mellitus, Type 2
dc.subject.mesh	Insulin Resistance
dc.subject.mesh	Diabetes Mellitus, Experimental
dc.subject.mesh	AMP-Activated Protein Kinases
dc.subject.mesh	Metformin
dc.subject.mesh	Animals
dc.subject.mesh	Rats
dc.subject.mesh	Diabetes Mellitus, Experimental
dc.subject.mesh	Diabetes Mellitus, Type 2
dc.subject.mesh	Insulin Resistance
dc.subject.mesh	Metformin
dc.subject.mesh	AMP-Activated Protein Kinases
dc.subject.mesh	Rats
dc.subject.mesh	Animals
dc.subject.mesh	Diabetes Mellitus, Type 2
dc.subject.mesh	Insulin Resistance
dc.subject.mesh	Diabetes Mellitus, Experimental
dc.subject.mesh	AMP-Activated Protein Kinases
dc.subject.mesh	Metformin
dc.title	New Treatment for Type 2 Diabetes Mellitus Using a Novel Bipyrazole Compound.
dc.type	Journal Article
utslib.citation.volume	12
utslib.location.activity	Switzerland
pubs.organisational-group	University of Technology Sydney
pubs.organisational-group	University of Technology Sydney/Faculty of Science
pubs.organisational-group	University of Technology Sydney/Faculty of Science/School of Life Sciences
utslib.copyright.status	open_access	*
dc.date.updated	2024-02-12T06:07:43Z
pubs.issue	2
pubs.publication-status	Published online
pubs.volume	12
utslib.citation.issue	2

Abstract:

2',3,3,5'-Tetramethyl-4'-nitro-2'H-1,3'-bipyrazole (TMNB) is a novel bipyrazole compound with unknown therapeutic potential in diabetes mellitus. This study aims to investigate the anti-diabetic effects of TMNB in a high-fat diet and streptozotocin-(HFD/STZ)-induced rat model of type 2 diabetes mellitus (T2D). Rats were fed HFD, followed by a single low dose of STZ (40 mg/kg). HFD/STZ diabetic rats were treated orally with TMNB (10 mg/kg) or (200 mg/kg) metformin for 10 days before terminating the experiment and collecting plasma, soleus muscle, adipose tissue, and liver for further downstream analysis. TMNB reduced the elevated levels of serum glucose in diabetic rats compared to the vehicle control group (p < 0.001). TMNB abrogated the increase in serum insulin in the treated diabetic group compared to the vehicle control rats (p < 0.001). The homeostasis model assessment of insulin resistance (HOMA-IR) was decreased in the diabetic rats treated with TMNB compared to the vehicle controls. The skeletal muscle and adipose tissue protein contents of GLUT4 and AMPK were upregulated following treatment with TMNB (p < 0.001, < 0.01, respectively). TMNB was able to upregulate GLUT2 and AMPK protein expression in liver (p < 0.001, < 0.001, respectively). LDL, triglyceride, and cholesterol were reduced in diabetic rats treated with TMNB compared to the vehicle controls (p < 0.001, 0.01, respectively). TMNB reduced MDA and IL-6 levels (p < 0.001), and increased GSH level (p < 0.05) in diabetic rats compared to the vehicle controls. Conclusion: TMNB ameliorates insulin resistance, oxidative stress, and inflammation in a T2D model. TMNB could represent a promising therapeutic agent to treat T2D.

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http://hdl.handle.net/10453/175586