Treating the Changing Face of Western Medicine: Pharmacological Interventions on the Jak/STAT Pathway in Diabetic Complications and its Relationship to Ageing
Abstract
Ageing and diabetes are two major healthcare concerns that used to be regarded as
problems of the Western world but are now of increasing concern in developing nations.
Treating elderly patients with diabetes poses issues for clinicians due to often complex, preexisting
drug regimes. Research targeted at the development of novel drugs that have
multiple effects on diabetes could go some way towards reducing polypharmacy in these
patients. Here I present evidence that the oral Jak1/3 inhibitor, baricitinib, has effects on
multiple aspects of diabetes. Baricitinib has been suggested to be a strong anti-inflammatory
given the role Jak plays in transducing cytokine signals to elicit immune cell activation and
maturation. Baricitinib was found to reduce urinary albumin to creatinine ratio and
mesangial expansion in mice on an experimental high-fat diet with a diabetic metabolic
profile when compared with naïve, non-diabetic mice. This reduction in renal impairment
from diabetes was not found with a large reduction in proinflammatory cytokines and
instead appears to be as a result of a direct effect on the cells of the mesangium. Baricitinib
also reduced the circulating levels of cholesterol with a positive effect on the LDL: HDL ratio
of diabetic mice. This reduction in cholesterol appears to be because of the abolition of GLP-
1 signalling, initiating an increase in blood insulin, preventing lipid flux and inhibiting LDL
formation. Both of these changes in key diabetic complications were not accompanied by an
increase in sensitivity to insulin compared with vehicle treated diabetic mice. These results
show that baricitinib has a beneficial effect on two key aspects of the diabetic condition but
that it does not modify insulin sensitivity itself. Baricitinib may represent a potential
treatment for these diabetes-associated pathologies but only in combination with traditional
anti-diabetic treatments.
Authors
Hull, William JohnCollections
- Theses [4143]