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Does sugar kill a roll?

http://stke.sciencemag.org/cgi/content/abstract/ajprenal;293/3/F877

Insulin causes renal dopamine D1 receptor desensitization via GRK2-mediated receptor phosphorylation involving phosphatidylinositol 3-kinase and protein kinase C

Anees Ahmad Banday, Fatima Rizwan Fazili, , and Mustafa F. Lokhandwala

Heart and Kidney Institute, College of Pharmacy, University of Houston, Houston, Texas

Received for publication 17 April 2007. Accepted for publication 9 June 2007.
Abstract: The renal dopamine system plays an important role in sodium homeostasis and a defect in dopamine D1 receptor (D1R) function is present in hypertension, diabetes, and aging. Our previous studies in hyperinsulinemic animals and in renal cell cultures treated with insulin showed decrease in D1R number and defective coupling to G proteins; however, the exact mechanisms remained unknown. Therefore, we investigated insulin-mediated D1R desensitization and underlying molecular mechanism in opossum kidney (OK) cells. Chronic exposure (24 h) of OK cells to 10 nM insulin caused significant decrease in D1R number and agonist affinity. The D1R was hyperserine phosphorylated, uncoupled from G proteins and SKF38393, a D1R agonist, failed to stimulate G proteins and inhibit Na-K-ATPase activity. Insulin increased protein kinase C (PKC) activity and caused G protein-coupled receptor kinase 2 (GRK2) translocation to the membranes. Tyrosine kinase inhibitor genistein and phosphatidylinositol 3-kinase (PI3K) inhibitor wortmannin blocked insulin-mediated PKC activation and GRK2 membranous translocation. In addition to genistein and wortmannin, GRK2 membranous tranlocation was also blocked by PKC inhibitor chelerythrine chloride and GRK2-specific siRNA. Genistein, wortmannin, chelerythrine chloride, and GRK2 siRNA abrogated D1R serine phosphorylation and normalized D1R expression and affinity in insulin-treated cells. Furthermore, these inhibitors and siRNA restored D1R G protein coupling and ability of SKF38393 to inhibit Na-K-ATPase activity. In conclusion, insulin-induced D1R desensitization involves PI3K, PKC, and GRK2. Insulin activates PI3K-PKC-GRK2 cascade, causing D1R serine phosphorylation, which leads to D1R downregulation and uncoupling from G proteins, and results in the failure of SKF38393 to stimulate G proteins and inhibit Na-K-ATPase activity.
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http://care.diabetesjournals.org/content/27/12/3020.full speaks about it. http://ccforum.com/content/11/2/R51 mentions at 6 in the introduction that adrenaline causes hyperglycemia, but other than that, i was just basing it on memory from a doctors drug advice when i was a teenager.

http://www.sciencedaily.com/releases/2007/10/071017090131.htm bit irrelevant but an interesting read.

Also, i'd been lead to believe that most forms of stress in some way raise the blood sugar levels? Periods of anxiety, and anxiety attacks, raise insulin resistance, again, according to my consultant. I have often found my blood sugars and my insulin resistance increased after an anxiety attack. Often having to increase my insulin to carb portion ratio from 1:1 (except when its 1.5:1 in the morning) to 1.5:1 or higher for a period after (if you are familiar with the DAFNE method and ratio control i guess). Although i've never done speed, every stimulant i've taken has given anxiety attack-like symptoms when coming up.
 
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also, i don't think it actually affects insulin release, but how well your body responds to the insulin present. i was only talking about insulin resistance not the release of insulin.
 
^ Say what?

Alcohol is one of the only drugs that doesn not combine wel with anything else....expect for benzos in low ammounts and opiates/oids.

Ethanol is a CNS depressant its binds to acetylcholine, setotonin, NMDA and GABAa receptors.
Add caffeine and taurine to that...and figure out yourself.

Plus alcohol is a dehydrating agent!
 
Yeah, the only drug I will ever have alcohol with is psylocybin mushrooms. :)
 
Nexius, !!! Of the thousands of abstracts I've read on ADD, that is by far the most arcane. I'm missing the connection between D1 receptor phosphorylation in the kidney and systemic insulin desensitization.

tvas, this is interesting stuff. I'm trying to tie together the somatic component of amphetamine crash, sugar crash, post-prandial anxiety, amphetamine withdrawal and my positive experiences with metformin while going through amphetamine withdrawal (I'm not diabetic). Thanks. Lots of stuff to look into here.
 
hmm, yeah it is an interesting and surprisingly little covered area. let me know if you come up with anything!
 
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