Research Article Details
| Article ID: | A52545 |
| PMID: | 25745813 |
| Source: | Gen Comp Endocrinol |
| Title: | Histomorphology of the bottlenose dolphin (Tursiops truncatus) pancreas and association of increasing islet β-cell size with chronic hypercholesterolemia. |
| Abstract: | Bottlenose dolphins (Tursiops truncatus) can develop metabolic states mimicking prediabetes, including hyperinsulinemia, hyperlipidemia, elevated glucose, and fatty liver disease. Little is known, however, about dolphin pancreatic histomorphology. Distribution and area of islets, α, β, and δ cells were evaluated in pancreatic tissue from 22 dolphins (mean age 25.7years, range 0-51). Associations of these measurements were evaluated by sex, age, percent high glucose and lipids during the last year of life, and presence or absence of fatty liver disease and islet cell vacuolation. The most common pancreatic lesions identified were exocrine pancreas fibrosis (63.6%) and mild islet cell vacuolation (47.4%); there was no evidence of insulitis or amyloid deposition, changes commonly associated with type 2 diabetes. Dolphin islet architecture appears to be most similar to the pig, where α and β cells are localized to the central or periphery of the islet, respectively, or are well dispersed throughout the islet. Unlike pigs, large islets (greater than 10,000μm(2)) were common in dolphins, similar to that found in humans. A positive linear association was identified between dolphin age and islet area average, supporting a compensatory response similar to other species. The strongest finding in this study was a positive linear association between islet size, specifically β-cells, and percent blood samples with high cholesterol (greater than 280mg/dl, R(2)=0.57). This study is the most comprehensive assessment of the dolphin pancreas to date and may help direct future studies, including associations between chronic hypercholesterolemia and β-cell size. |
| DOI: | 10.1016/j.ygcen.2015.02.023 |
| Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs | |
|---|---|---|---|---|---|
| S01 | Improve insulin resistance | insulin sensitizer; insulin resistance; glucose tolerance | Biguanide: increases 5-AMP activated protein kinase signaling; SGLT-2 inhibitor; Thiazalidinedione: selective PPAR-γ agonists; GLP-1 agonist | Metformin; Empagliflozin; Canagliflozin; Rosiglitazone; Pioglitazone; Liraglutide | Details |
| S03 | Anti-fibrosis | fibrosis | Angiotensin Receptor Blocker (ARB); CCR2/CCR5 antagonist; Thyroid receptor β agonist; PEGylated human FGF21 analogue; Monoclonal antibody to lysyl oxidase-like 2 (LOXL2); Galectin-3 inhibitor; FGF19 variant | Losartan; Cenicriviroc; VK-2809; MGL-3196; Pegbelfermin; Simtuzumab; GR-MD-02; NGM282 | Details |
| Target ID | Target Name | GENE | Action | Class | UniProtKB ID | Entry Name |
|---|
| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| I13 | 3146 | Lipid metabolism disorder | An inherited metabolic disorder that involves the creation and degradation of lipids. http://en.wikipedia.org/wiki/Lipid_metabolism | disease of metabolism/ inherited metabolic disorder | Details |
| I05 | 9352 | Type 2 diabetes mellitus | A diabetes that is characterized by chronic hyperglycaemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion, insulin action, or both. A diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. http://en.wikipedia.org/wiki/Diabetes, http://en.wikipedia.org/wiki/Diabetes_mellitus_type_2 | disease of metabolism/inherited metabolic disorder/ carbohydrate metabolic disorder/glucose metabolism disease/diabetes/ diabetes mellitus | Details |
| Drug ID | Drug Name | Type | DrugBank ID | Targets | Category | Latest Progress | |
|---|---|---|---|---|---|---|---|
| D545 | Pig placenta extract | Biological extract | -- | -- | -- | Under clinical trials | Details |
| D579 | Emfilermin | Miscellany | -- | adipocytes | Enhance lipid metabolism | Under investigation | Details |
| D182 | Insulin | Biological drug | DB00030 | INSR agonist; CPE modulator&product of | -- | Under clinical trials | Details |
| D248 | Obeticholic Acid | Chemical drug | DB05990 | NR1H4 activator; NR1H4 agonist; FXR agonist | Enhance lipid metabolism | Approval rejected | Details |
| D316 | S-adenosyl-L-methionine | Chemical drug | DB00118 | GNMT cofactor | Antiviral | Under clinical trials | Details |
| D094 | Cysteamine | Chemical drug | DB00847 | GSS stimulant | Renal drug | Under clinical trials | Details |
| D095 | Cysteamine bitartrate | Chemical drug | DB00847 | -- | -- | Under clinical trials | Details |