Browse
Search for other papers by Sandra K Szlapinski in
Google Scholar
PubMed
Physiology and Pharmacology, Western University, London, Ontario, Canada
Search for other papers by David J Hill in
Google Scholar
PubMed
Insulin resistance contributes to the development of various diseases, including type 2 diabetes and gestational diabetes. Even though gestational diabetes is specific to pregnancy, it can result in long-term glucose intolerance and type 2 diabetes after delivery. Given the substantial health and economic burdens associated with diabetes, it is imperative to better understand the mechanisms leading to insulin resistance and type 2 diabetes so that treatments targeted at reversing symptoms can be developed. Considering that the endocrine cells of the pancreas (islets of Langerhans) largely contribute to the pathogenesis of diabetes (beta-cell insufficiency and dysfunction), the elucidation of the various mechanisms of endocrine cell plasticity is important to understand. By better defining these mechanisms, targeted therapeutics can be developed to reverse symptoms of beta-cell deficiency and insulin resistance in diabetes. Animal models play an important role in better understanding these mechanisms, as techniques for in vivo imaging of endocrine cells in the pancreas are limited. Therefore, this review article will discuss the available rodent models of gestational and type 2 diabetes that are characterized by endocrine cell impairments in the pancreas, discuss the models with a comparison to human diabetes, and explore the potential mechanisms of endocrine cell plasticity that contribute to these phenotypes, as these mechanisms could ultimately be used to reverse blood glucose dysregulation in diabetes.
Institute of Medical Sciences, University of Toronto, Toronto, Ontario, Canada
Department of Pharmacology, University of Toronto, Toronto, Ontario, Canada
Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada
Banting & Best Diabetes Centre, Toronto, Ontario, Canada
Search for other papers by Margaret K Hahn in
Google Scholar
PubMed
Banting & Best Diabetes Centre, Toronto, Ontario, Canada
Department of Physiology, University of Toronto, Toronto, Ontario, Canada
Search for other papers by Adria Giacca in
Google Scholar
PubMed
Department of Physiology, University of Toronto, Toronto, Ontario, Canada
Search for other papers by Sandra Pereira in
Google Scholar
PubMed
Metabolic tests are vital to determine in vivo insulin sensitivity and glucose metabolism in preclinical models, usually rodents. Such tests include glucose tolerance tests, insulin tolerance tests, and glucose clamps. Although these tests are not standardized, there are general guidelines for their completion and analysis that are constantly being refined. In this review, we describe metabolic tests in rodents as well as factors to consider when designing and performing these tests.
CIBB - Center for Innovative Biomedicine and Biotechnology, University of Coimbra, Coimbra, Portugal
Department of Life Sciences, Faculty of Science and Technology, University of Coimbra, Coimbra, Portugal
Search for other papers by Aryane Cruz Oliveira Pinho in
Google Scholar
PubMed
CIBB - Center for Innovative Biomedicine and Biotechnology, University of Coimbra, Coimbra, Portugal
Flow Cytometry Unit, Department of Clinical Pathology, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal
Coimbra Institute for Clinical and Biomedical Research (iCBR), Group of Environmental Genetics of Oncobiology (CIMAGO), Faculty of Medicine (FMUC), University of Coimbra, Coimbra, Portugal
Clinical Academic Center of Coimbra (CACC), Coimbra, Portugal
Search for other papers by Paula Laranjeira in
Google Scholar
PubMed
CIBB - Center for Innovative Biomedicine and Biotechnology, University of Coimbra, Coimbra, Portugal
Institute for Interdisciplinary Research, University of Coimbra (IIIUC), Casa Costa Alemão, Coimbra, Portugal
APDP-Portuguese Diabetes Association, Lisbon, Portugal
Search for other papers by Eugenia Carvalho in
Google Scholar
PubMed
Despite the known link between obesity and insulin resistance (IR) to chronic low-grade inflammation, new markers capable of early IR detection are needed. Immune cells are components of adipose tissue’s (AT) stromal vascular fraction (SVF) that regulate AT homeostasis. The altered phenotype and function of AT-infiltrating immune cells may contribute to the development and maintenance of local AT inflammation observed under obesity-induced IR conditions. Impaired AT-specific immunometabolic function may influence the whole organism. Therefore, AT-infiltrating immune cells may be important players in the development of obesity-related metabolic complications, such as type 2 diabetes mellitus (T2DM). B and T cells, particularly CD20+ T cells, play important roles in human pathology, such as autoimmune disease and cancer. However, the question remains as to whether CD20+ T cells have an important contribution to the development of obesity-related IR. While circulating CD20+ T cells are mostly of the central memory phenotype (i.e. antigen-experienced T cells with the ability to home to secondary lymphoid organs), tissues-infiltrated CD20+ T cells are predominantly of the effector memory phenotype (i.e. antigen-experienced T cells that preferentially infiltrate peripheral tissues). The latter produce pro-inflammatory cytokines, such as IFN-γ and IL-17, which play a role in obesity-related IR development. This review describes the CD20 molecule and its presence in both B and T cells, shedding light on its ontogeny and function, in health and disease, with emphasis on AT. The link between CD20+ T cell dysregulation, obesity, and IR development supports the role of CD20+ T cells as markers of adipose tissue dysmetabolism.
Search for other papers by Charlotte Steenblock in
Google Scholar
PubMed
Search for other papers by Nicole Bechmann in
Google Scholar
PubMed
Search for other papers by Felix Beuschlein in
Google Scholar
PubMed
Search for other papers by Christian Wolfrum in
Google Scholar
PubMed
Department of Endocrinology, Diabetology and Clinical Nutrition, University Hospital Zurich (USZ) and University of Zurich (UZH), Zürich, Switzerland
School of Cardiovascular and Metabolic Medicine and Sciences, Faculty of Life Sciences & Medicine, King’s College London, London, UK
Search for other papers by Stefan R Bornstein in
Google Scholar
PubMed
Obesity is associated with a higher risk of severe coronavirus disease 2019 (COVID-19) and increased mortality. In the current study, we have investigated the expression of ACE2, NRP1, and HMGB1, known to facilitate severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) cell entry, in adipose tissue from non-COVID-19 control patients with normal weight, overweight, and obesity. All factors were expressed, but no significant differences between the groups were observed. Furthermore, diabetes status and medications did not affect the expression of ACE2. Only in obese men, the expression of ACE2 in adipose tissue was higher than in obese women. In the adipose tissue from patients who died from COVID-19, SARS-CoV-2 was detected in the adipocytes even though the patients died more than 3 weeks after the acute infection. This suggests that adipocytes may act as reservoirs for the virus. In COVID-19 patients, the expression of NRP1 was increased in COVID-19 patients with overweight and obesity. Furthermore, we observed an increased infiltration with macrophages in the COVID-19 adipose tissues compared to control adipose tissue. In addition, crown-like structures of dying adipocytes surrounded by macrophages were observed in the adipose tissue from COVID-19 patients. These data suggest that in obese individuals, in addition to an increased mass of adipose tissue that could potentially be infected, increased macrophage infiltration due to direct infection with SARS-CoV-2 and sustained viral shedding, rather than preinfection ACE2 receptor expression, may be responsible for the increased severity and mortality of COVID-19 in patients with obesity.
