Friday, May 31, 2019

High uric acid directly inhibits insulin signaling and induces insulin resistance

Accumulating clinical evidence suggests that hyperuricemia is strongly associated with abnormal glucose metabolism and insulin resistance. However, how high uric acid (HUA) level causes insulin resistance remains unclear. We aimed to determine the direct role of HUA in insulin resistance in vitro and in vivo in mice.

An acute hyperuricemia mouse model was created by potassium oxonate treatment, and the impact of HUA level on insulin resistance was investigated by glucose tolerance test, insulin tolerance test and insulin signaling, including phosphorylation of insulin receptor substrate 1 (IRS1) and Akt. HepG2 cells were exposed to HUA treatment and N-acetylcysteine (NAC), reactive oxygen species scavenger; IRS1 and Akt phosphorylation was detected by Western blot analysis after insulin treatment.

Hyperuricemic mice showed impaired glucose tolerance with insulin resistance. Hyperuricemia inhibited phospho-Akt (Ser473) response to insulin and increased phosphor-IRS1 (Ser307) in liver, muscle and fat tissues. HUA induced oxidative stress, and the antioxidant NAC blocked HUA-induced IRS1 activation and Akt inhibition in HepG2 cells.

This study supplies the first evidence of HUA directly inducing insulin resistance in vivo and in vitro. Increased uric acid level may inhibit IRS1 and Akt insulin signalling and induce insulin resistance. The reactive oxygen species pathway plays a key role in HUA-induced insulin resistance.

My Take:
This is the abstract straight from PubMed. This study was mentioned in a seminar I took on blood chemistries last month.

Measurement of uric acid levels used to be a common component of routine laboratory testing. However, I rarely see the UA levels as a part of a comprehensive metabolic profile. I added it back to my routine testing a few years ago.

It has long been known that insulin resistance and diabetes causes kidney damage. We now know that the reverse is also true – loss of kidney function can cause insulin resistance and lead to diabetes.

In addition to looking at the BUN (blood urea nitrogen), creatinine, and uric acid on your yearly lab work, pay close attention to the eGFR (estimated glomerular filtration rate). I have written several blogs about this test, so please type “GFR” in the search box in the upper left hand corner of my blog site to review previous blogs on this topic.

An eGFR below 60 indicates kidney damage. However, an eGFR between 60 and 95 indicates loss of kidney function. Medically this functional loss is typically ignored. Some labs still list the result as <59 95.="" a="" and="" any="" assign="" b="" don="" egfr="" ignore="" less="" number="" please="" rather="" review="" t="" test.="" than="" the="" to="" value="" your="">Bottom Line:
high uric acid is an important factor in the onset of insulin resistance and diabetes. Please have your uric acid levels checked as a part of your yearly physical and address any abnormal findings with your physician.

May 14, 2014 NIH

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