The many faces of diabetes. Is there a need for re-classification? A narrative review

Sakran, Nasser; Graham, Yitka; Pintar, Tadeja; Yang, Wah; Kassir, Radwan; Willigendael, Edith M.; Singhal, Rishi; Kooreman, Zoë E.; Ramnarain, Dharmanand; Mahawar, Kamal; Parmar, Chetan; Madhok, Brijesh; Pouwels, Sjaak

doi:10.1186/s12902-021-00927-y

Cited by 23 publications

(11 citation statements)

References 141 publications

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“…Obesity is associated with impaired glucose tolerance, often leading to type 2 diabetes mellitus (T2DM). T2DM, which constitutes 90% to 95% of all cases of diabetes, is characterized by decreased insulin sensitivity in peripheral tissues such as adipose tissue, skeletal muscles, or liver, as well as a progressive loss of proper insulin secretion [ 41 ]. T2DM reduces functional capacities and quality of life, dramatically increasing morbidity and premature mortality [ 42 ].…”

Section: Admscs In the Treatment Of Obesity And Its Metabolic Complic...mentioning

confidence: 99%

Gene Therapy Based on Mesenchymal Stem Cells Derived from Adipose Tissue for the Treatment of Obesity and Its Metabolic Complications

Lopez-Yus

García-Sobreviela

Moral

et al. 2023

IJMS

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Obesity is a highly prevalent condition often associated with dysfunctional adipose tissue. Stem cell-based therapies have become a promising tool for therapeutic intervention in the context of regenerative medicine. Among all stem cells, adipose-derived mesenchymal stem cells (ADMSCs) are the most easily obtained, have immunomodulatory properties, show great ex vivo expansion capacity and differentiation to other cell types, and release a wide variety of angiogenic factors and bioactive molecules, such as growth factors and adipokines. However, despite the positive results obtained in some pre-clinical studies, the actual clinical efficacy of ADMSCs still remains controversial. Transplanted ADMSCs present a meager rate of survival and proliferation, possibly because of the damaged microenvironment of the affected tissues. Therefore, there is a need for novel approaches to generate more functional ADMSCs with enhanced therapeutic potential. In this context, genetic manipulation has emerged as a promising strategy. In the current review, we aim to summarize several adipose-focused treatments of obesity, including cell therapy and gene therapy. Particular emphasis will be given to the continuum from obesity to metabolic syndrome, diabetes, and underlying non-alcoholic fatty liver disease (NAFLD). Furthermore, we will provide insights into the potential shared adipocentric mechanisms involved in these pathophysiological processes and their remediation using ADMSCs.

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Section: Admscs In the Treatment Of Obesity And Its Metabolic Complic...mentioning

confidence: 99%

Gene Therapy Based on Mesenchymal Stem Cells Derived from Adipose Tissue for the Treatment of Obesity and Its Metabolic Complications

Lopez-Yus

García-Sobreviela

Moral

et al. 2023

IJMS

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“…Diabetes is one of the most common metabolic disorders with chronic impacts. Diabetes is a broader term which encompasses the group of diseases that manifest impairment in glucose utilization [ 220 ]. In general, chronic diabetes is categorized as type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) whereas T1DM is characterized by defective insulin synthesis primarily due to pancreatic β-cell destruction whereas T2DM is characterized by progressive loss in insulin secretion along with insulin insensitivity [ 221 , 222 ].…”

Section: Lncrnas In Human Diseasesmentioning

confidence: 99%

Signaling by LncRNAs: Structure, Cellular Homeostasis, and Disease Pathology

Nadhan

Isidoro

Song

et al. 2022

Cells

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The cellular signaling network involves co-ordinated regulation of numerous signaling molecules that aid the maintenance of cellular as well as organismal homeostasis. Aberrant signaling plays a major role in the pathophysiology of many diseases. Recent studies have unraveled the superfamily of long non-coding RNAs (lncRNAs) as critical signaling nodes in diverse signaling networks. Defective signaling by lncRNAs is emerging as a causative factor underlying the pathophysiology of many diseases. LncRNAs have been shown to be involved in the multiplexed regulation of diverse pathways through both genetic and epigenetic mechanisms. They can serve as decoys, guides, scaffolds, and effector molecules to regulate cell signaling. In comparison with the other classes of RNAs, lncRNAs possess unique structural modifications that contribute to their diversity in modes of action within the nucleus and cytoplasm. In this review, we summarize the structure and function of lncRNAs as well as their vivid mechanisms of action. Further, we provide insights into the role of lncRNAs in the pathogenesis of four major disease paradigms, namely cardiovascular diseases, neurological disorders, cancers, and the metabolic disease, diabetes mellitus. This review serves as a succinct treatise that could open windows to investigate the role of lncRNAs as novel therapeutic targets.

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“…3 Insulin is released by the β-cells of the islets of Langerhans nested within the pancreas, which, upon mixing with the bloodstream, reduces the blood sugar levels by a combination of mechanisms, including glycogenesis. 4,5 It was discovered in 1921 by a team of Canadian researchers: Frederick Banting, Charles Best, and John Macleod and purified later by James Collip. The discovery was subsequently recognized with a Nobel Prize in Physiology or Medicine (1923) to Banting and Macleod, who shared their awards with Best and Collip, respectively.…”

Section: Introductionmentioning

confidence: 99%

An Investigation into the Acidity-Induced Insulin Agglomeration: Implications for Drug Delivery and Translation

Fagihi,

Premathilaka,

O’Neill

et al. 2023

ACS Omega

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Insulin undergoes agglomeration with (subtle) changes in its biochemical environment, including acidity, application of heat, ionic imbalance, and exposure to hydrophobic surfaces. The therapeutic impact of such unwarranted insulin agglomeration is unclear and needs further evaluation. A systematic investigation was conducted on recombinant human insulinwith or without labeling with fluorescein isothiocyanatewhile preparing insulin suspensions (0.125, 0.25, and 0.5 mg/mL) at pH 3. The suspensions were incubated (37 °C) and analyzed at different time points (t = 2, 4, 24, 48, and 72 h). Transmission electron microscopy and nanoparticle tracking analysis identified colloidally stable (zeta potential 15 ± 5 mV) spherical agglomerates of unlabeled insulin (100–500 nm). Circular dichroism established the preservation of insulin’s secondary structure rich in α-helices despite exposure to an acidic environment (pH 3) for 72 h. Furthermore, fluorescence lifetime imaging microscopy illustrated an acidic core inside these spherical agglomerates, while the acidity gradually lessened toward the periphery. Some of these smaller agglomerates fused to form larger chunks with discrete zones of acidity. The data indicated a primary nucleation-driven mechanism of acid-induced insulin agglomeration under physiologically relevant conditions.

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The many faces of diabetes. Is there a need for re-classification? A narrative review

Cited by 23 publications

References 141 publications

Gene Therapy Based on Mesenchymal Stem Cells Derived from Adipose Tissue for the Treatment of Obesity and Its Metabolic Complications

Gene Therapy Based on Mesenchymal Stem Cells Derived from Adipose Tissue for the Treatment of Obesity and Its Metabolic Complications

Signaling by LncRNAs: Structure, Cellular Homeostasis, and Disease Pathology

An Investigation into the Acidity-Induced Insulin Agglomeration: Implications for Drug Delivery and Translation

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