β-Cell Fate in Human Insulin Resistance and Type 2 Diabetes: A Perspective on Islet Plasticity
| Autor: | Teresa Mezza, Francesca Cinti, Rohit N. Kulkarni, Chiara Maria Assunta Cefalo, Andrea Giaccari, Alfredo Pontecorvi |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Endocrinology Diabetes and Metabolism medicine.medical_treatment Cell Plasticity 030209 endocrinology & metabolism trans-differentiation Type 2 diabetes Biology 03 medical and health sciences Islets of Langerhans 0302 clinical medicine Insulin resistance Diabetes mellitus Insulin-Secreting Cells insulin resistance Insulin Secretion Internal Medicine medicine insulin resistance trans-differentiation dedifferentiation human type 2 diabetes mellitus personalized medicine Humans Secretion geography geography.geographical_feature_category Insulin Transdifferentiation dedifferentiation human type 2 diabetes mellitus Settore MED/13 - ENDOCRINOLOGIA Organ Size personalized medicine Cell Dedifferentiation medicine.disease Islet 030104 developmental biology Diabetes Mellitus Type 2 Glucagon-Secreting Cells Cell Transdifferentiation Neuroscience Methodology Review |
| Zdroj: | Diabetes |
| Popis: | Although it is well established that type 2 diabetes (T2D) is generally due to the progressive loss of β-cell insulin secretion against a background of insulin resistance, the actual correlation of reduced β-cell mass to its defective function continues to be debated. There is evidence that a compensatory increase in β-cell mass, and the consequent insulin secretion, can effectively cope with states of insulin resistance, until hyperglycemia supervenes. Recent data strongly indicate that the mechanisms by which islets are able to compensate in response to insulin resistance in peripheral tissues is secondary to hyperplasia, as well as the activation of multiple cellular machineries with diverse functions. Importantly, islet cells exhibit plasticity in altering their endocrine commitment; for example, by switching from secretion of glucagon to secretion of insulin and back (transdifferentiation) or from an active secretory state to a nonsecretory quiescent state (dedifferentiation) and back. Lineage tracing (a method used to track each cell though its differentiation process) has demonstrated these potentials in murine models. A limitation to drawing conclusions from human islet research is that most studies are derived from human autopsy and/or organ donor samples, which lack in vivo functional and metabolic profiling. In this review, we specifically focus on evidence of islet plasticity in humans—from the normal state, progressing to insulin resistance to overt T2D—to explain the seemingly contradictory results from different cross-sectional studies in the literature. We hope the discussion on this intriguing scenario will provide a forum for the scientific community to better understand the disease and in the long term pave the way for personalized therapies. |
| Databáze: | OpenAIRE |
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