Modulation of G-protein expression and adenylyl cyclase signaling by high glucose in vascular smooth muscle*1
Bibliographic record
Abstract
OBJECTIVE: We have recently shown a decreased expression of Gialpha proteins and associated functions in aorta from short term (5 days) streptozotocin-induced diabetic rats. Since hyperglycemia is one of the underlying causes of diabetes-induced cardiovascular complications, it was of interest to examine if hyperglycemia may play a direct role in down regulating the expression of Gialpha in vascular smooth muscle cells of diabetic subjects. For this, the effect of high glucose treatment on Gialpha protein expression and adenylyl cyclase signaling in intact aorta and vascular smooth muscle cells (A10 cells) was investigated. METHODS: The cells were grown in normal glucose (5.5 mM) medium and were subsequently exposed to high glucose (26 mM) or normal medium for various time periods (24-96 h). Aorta from control rats were exposed to normal and high glucose medium for 72 h. The levels of G-proteins were determined by immunoblotting using specific antibodies. Adenylyl cyclase activity stimulated or inhibited by agonists was determined to examine the functions of G-proteins. RESULTS: The levels of Gialpha-2 and Gialpha-3 proteins in membranes from A10 cells and aorta exposed to high glucose for 3 or 4 days were significantly decreased as compared to control cells and control aorta, respectively, whereas the levels of Gsalpha protein were not altered. In addition, receptor-dependent and -independent functions of Gialpha proteins were attenuated in hyperglycemic cells, as demonstrated by inhibition of forskolin (FSK)-stimulated adenylyl cyclase activity by low concentration of GTPgammaS or by angiotensin II (Ang II), oxotremorine or C-ANP(4-23) (a ring deleted analog of atrial natriuretic peptide). On the other hand, the stimulatory effects of GTPgammaS, glucagon, isoproterenol, FSK and sodium fluoride on adenylyl cyclase were significantly augmented in hyperglycemic cells as compared to control cells, whereas basal adenylyl cyclase activity was significantly lower in hyperglycemic cells as compared to control cells. CONCLUSION: These results indicate that high glucose decreased the levels and functions of Gi proteins in A10 VSMC and aorta. It may thus be suggested that decreased levels and activity of Gi proteins and adenylyl cyclase signaling induced by hyperglycemia may be one of the important mechanisms contributing to the cardiovascular complications associated with diabetes.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".