Insulinoma-derived pseudo-islets for diabetes research

2021 ◽  
Author(s):  
Nathaniel J. Hart ◽  
Craig Weber ◽  
Nicholas Price ◽  
Alma Banuelos ◽  
Madison Schultz ◽  
...  
Keyword(s):  
Average Diameter ◽  
Human Islets ◽  
Whole Body ◽  
Diabetes Research ◽  
Rat Islets ◽  
Insulinoma Cell ◽  
Islet Morphology ◽  
Cell Propagation ◽  
Rat Insulinoma Cell Line ◽  
And Function

The islets of Langerhans of the pancreas are the primary endocrine organ responsible for regulating whole body glucose homeostasis. The use of isolated primary islets for research development and training requires organ resection, careful digestion and isolation of the islets from non-endocrine tissue. This process is time consuming, expensive and requires substantial expertise. For these reasons, we sought to develop a more rapidly obtainable and consistent model system with characteristic islet morphology and function that could be employed to train personnel and better inform experiments prior to using isolated rodent and human islets. Immortalized β cell lines reflect several aspects of primary β cells, but cell propagation in monolayer cell culture limits their usefulness in several areas of research which depend on islet morphology and/or functional assessment. In this manuscript we describe the propagation and characterization of insulinoma pseudo-islets (IPIs) from a rat insulinoma cell line INS832/3. IPIs were generated with an average diameter of 200 μm, consistent with general islet morphology. The rates of oxygen consumption and mitochondrial oxidation-reduction changes in response to glucose and metabolic modulators were similar to isolated rat islets. In addition, the dynamic insulin secretory patterns of IPIs were similar to primary rat islets. Thus, INS832/3-derived IPIs provide a valuable and convenient model for accelerating islet and diabetes research.

scholarly journals Exercise, Pharmaceutical Therapies and Type 2 Diabetes: Looking beyond Glycemic Control to Whole Body Health and Function

2021 ◽  
pp. 33-42
Author(s):  
Thomas Yates ◽  
Joseph Henson ◽  
Jack Sargeant ◽  
James A King ◽  
Ehtasham Ahmad ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Weight Loss ◽  
Glycemic Control ◽  
Research Center ◽  
Whole Body ◽  
Diabetes Research ◽  
University Hospitals ◽  
Glucose Lowering ◽  
And Function

Exercise, Pharmaceutical Therapies and Type 2 Diabetes: Looking beyond Glycemic Control to Whole Body Health and Function Thomas Yates()1,2, Joseph Henson1,2, Jack Sargeant1,2, James A King2,4, Ehtasham Ahmad1, Francesco Zaccardi1,3 and Melanie J Davies1,2  1Diabetes Research Center, University of Leicester, Leicester General Hospital, Leicester, LE5 4PW, UK 2NIHR Leicester Biomedical Research Center, University Hospitals of Leicester NHS Trust and University of Leicester, UK 3Leicester Real World Evidence Unit, Diabetes Research Center, University of Leicester, Leicester, UK 4National Center for Sport and Exercise Medicine, School of Sport, Exercise and Health Sciences, Loughborough University, UK © The Authors   Abstract Exercise is a powerful therapy for improving glycemic control and increasing cardiorespiratory fitness in adults with type 2 diabetes mellitus (T2DM). However, there is a dearth of evidence investigating interactions or synergies between exercise and most pharmaceutical therapies. This is important as exercise is rarely prescribed in isolation of other background medications used to manage T2DM. Therefore understanding which exercise and drug combinations optimize or blunt responses is crucial. This narrative review discusses advances in weight loss management in diabetes and highlights research opportunities and challenges for combining exercise therapies with newer generations of glucose-lowering therapies with weight loss effects, particularly glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter 2 inhibitors (SGLT2is). We discuss the role of exercise in preserving lean mass and increasing physical function along with other potential areas of synergy. We conclude that until the evidence base investigating areas of interaction or synergy between exercise and other glucose-lowering or weight loss therapies is developed, exercise will remain a generic rather than a tailored therapy in the management of T2DM. 

scholarly journals The Interplay between Mitochondrial Morphology and Myomitokines in Aging Sarcopenia

2020 ◽  
Vol 22 (1) ◽  
pp. 91
Author(s):  
Vanina Romanello
Keyword(s):  
Mitochondrial Dysfunction ◽  
Poor Quality ◽  
Whole Body ◽  
Fibroblast Growth Factor 21 ◽  
Mitochondrial Morphology ◽  
Mass Force ◽  
Major Mechanism ◽  
Muscle Aging ◽  
And Function

Sarcopenia is a chronic disease characterized by the progressive loss of skeletal muscle mass, force, and function during aging. It is an emerging public problem associated with poor quality of life, disability, frailty, and high mortality. A decline in mitochondria quality control pathways constitutes a major mechanism driving aging sarcopenia, causing abnormal organelle accumulation over a lifetime. The resulting mitochondrial dysfunction in sarcopenic muscles feedbacks systemically by releasing the myomitokines fibroblast growth factor 21 (FGF21) and growth and differentiation factor 15 (GDF15), influencing the whole-body homeostasis and dictating healthy or unhealthy aging. This review describes the principal pathways controlling mitochondrial quality, many of which are potential therapeutic targets against muscle aging, and the connection between mitochondrial dysfunction and the myomitokines FGF21 and GDF15 in the pathogenesis of aging sarcopenia.

Structure and Function of the Lateral Giant Neurone of the Primitive Crustacean Anaspides Tasmaniae

1979 ◽  
Vol 78 (1) ◽  
pp. 121-136
Author(s):  
GERALD E. SILVEY ◽  
IAN S. WILSON
Keyword(s):  
Action Potentials ◽  
Tactile Stimulation ◽  
Large Diameter ◽  
Whole Body ◽  
Giant Fibre ◽  
Single Action ◽  
Giant Neurone ◽  
And Function ◽  
Thoracic And Abdominal ◽  
Stimulation Of

The syncarid crustacean Anaspides tasmaniae rapidly flexes its free thoracic and abdominal segments in response to tactile stimulation of its body. This response decrements but recovers in slightly more than one hour. The fast flexion is evoked by single action potentials in the lateral of two large diameter fibres (40 μm) which lie on either side of the cord. The lateral giant fibre is made up of fused axons of 11 neurones, one in each of the last 5 thoracic and 6 abdominal ganglia. The soma of each neurone lies contralateral to the axon. Its neurite crosses that of its counterpart in the commissure and gives out dendrites into the neuropile of each hemiganglion. The lateral giant neurone receives input from the whole body but fires in response only to input from the fourth thoracic segment posteriorly. Both fibres respond with tactile stimulation of only one side. Since neither current nor action potentials spread from one fibre to the other, afferents must synapse with both giant neurones. The close morphological and physiological similarities of the lateral giant neurone in Anaspides to that in the crayfish (Eucarida) suggest that the lateral giant system arose in the ancestor common to syncarids and eucarids, prior to the Carboniferous.

scholarly journals Hypoxia-Preconditioned Wharton’s Jelly-Derived Mesenchymal Stem Cells Mitigate Stress-Induced Apoptosis and Ameliorate Human Islet Survival and Function in Direct Contact Coculture System

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Somayeh Keshtkar ◽  
Maryam Kaviani ◽  
Zahra Jabbarpour ◽  
Fatemeh Sabet Sarvestani ◽  
Mohammad Hossein Ghahremani ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Human Islets ◽  
Wharton’S Jelly ◽  
Isolated Pancreatic Islets ◽  
Wharton's Jelly ◽  
Coculture System ◽  
Induced Apoptosis ◽  
And Function ◽  
Islet Survival

Protection of isolated pancreatic islets against hypoxic and oxidative damage-induced apoptosis is essential during a pretransplantation culture period. A beneficial approach to maintain viable and functional islets is the coculture period with mesenchymal stem cells (MSCs). Hypoxia preconditioning of MSCs (Hpc-MSCs) for a short time stimulates the expression and secretion of antiapoptotic, antioxidant, and prosurvival factors. The aim of the present study was to evaluate the survival and function of human islets cocultured with Hpc-MSCs. Wharton’s jelly-derived MSCs were subjected to hypoxia (5% O2: Hpc) or normoxia (20% O2: Nc) for 24 hours and then cocultured with isolated human islets in direct and indirect systems. Assays of viability and apoptosis, along with the production of reactive oxygen species (ROS), hypoxia-inducible factor 1-alpha (HIF-1α), apoptotic pathway markers, and vascular endothelial growth factor (VEGF) in the islets, were performed. Insulin and C-peptide secretions as islet function were also evaluated. Hpc-MSCs and Nc-MSCs significantly reduced the ROS production and HIF-1α protein aggregation, as well as downregulation of proapoptotic proteins and upregulation of antiapoptotic marker along with increment of VEGF secretion in the cocultured islet. However, the Hpc-MSCs groups were better than Nc-MSCs cocultured islets. Hpc-MSCs in both direct and indirect coculture systems improved the islet survival, while promotion of function was only significant in the direct cocultured cells. Hpc potentiated the cytoprotective and insulinotropic effects of MSCs on human islets through reducing stressful markers, inhibiting apoptosis pathway, enhancing prosurvival factors, and promoting insulin secretion, especially in direct coculture system, suggesting the effective strategy to ameliorate the islet quality for better transplantation outcomes.

Calmodulin-Binding Proteins in a Cloned Rat Insulinoma Cell Line

Diabetes ◽  
1983 ◽  
Vol 32 (12) ◽  
pp. 1126-1133 ◽  
Author(s):  
T. Y. Nelson ◽  
J. M. Oberwetter ◽  
J. G. Chafouleas ◽  
A. E. Boyd
Keyword(s):  
Cell Line ◽  
Binding Proteins ◽  
Calmodulin Binding ◽  
Insulinoma Cell ◽  
Insulinoma Cell Line ◽  
Rat Insulinoma Cell Line ◽  
Rat Insulinoma
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