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The Effects of 4‐Methylumbelliferone (4‐MU) on Hyperglycemia in Type 2 Diabetic Mice
Author(s) -
Edwards Jasmine Sheria,
Sunkari Vivekananda,
Bollyky Paul
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.701.4
Subject(s) - insulin , glycemic , medicine , type 2 diabetes , endocrinology , diabetes mellitus , ex vivo , islet , in vivo , pancreatic islets , pharmacology , chemistry , in vitro , biology , biochemistry , microbiology and biotechnology
Hyperglycemia is the underlying condition in diabetes that is associated with increase in morbidity and mortality. There is a need for other and more cost‐effective treatments directed at regulating blood‐glucose levels. Hyaluronan (HA) is an extracellular matrix component linked to diabetes. Higher concentrations of HA are found in the pancreatic islets and serum of individuals with Type 2 Diabetes (T2D). Based on these findings we hypothesized that inhibition of HA synthesis can lead to improved glycemic control in Type II Diabetics. To determine the effects of HA inhibition in T2D, 4‐Methylumbelliferone (4‐MU) was used to treat diabetic mice. Diabetic mice fed 4‐MU rapidly (<48 hours) became normoglycemic and maintained glycemic control through the duration of the experiment. These animals demonstrated a significant decrease in blood‐glucose and a partial decrease in weight. Quantification of insulin by enzyme‐linked immunosorbent assay (ELISA) showed that both serum and islets cultures from 4‐MU treated mice exhibited increased insulin production. Consistent with this data, mice lacking CD44 (HA receptor) show higher levels of insulin production while islets from CD44 −/− mice produce more insulin in response to glucose challenge ex vivo . This data indicates that HA is increased in T2D and negatively regulates insulin production in a CD44‐dependent manner. We propose that 4‐MU, the active ingredient in a drug called “hymecromone” that is currently approved to treat biliary spasm, could be repurposed to treat hyperglycemia in T2D. Support or Funding Information This work was supported in part by National Institutes of Health grants and a BIRT supplement. This work was also supported by grants from the Juvenile Diabetes Research Foundation and Larry L Hillblom foundation fellowship.