Abstract: TH-PO683
Intestine Can Modulate Diabetes in Renal Failure (RF) in Animals
Session Information
- Diabetes Mellitus and Obesity: Basic - Experimental - I
November 02, 2017 | Location: Hall H, Morial Convention Center
Abstract Time: 10:00 AM - 10:00 AM
Category: Diabetes
- 501 Diabetes Mellitus and Obesity: Basic - Experimental
Authors
- Ghosh, Siddhartha S., VCU Medical Ctr, Richmond, Virginia, United States
- Gonzalez, Austin J, Virginia Commonwealth University, Fredericksburg, Virginia, United States
- Carl, Daniel E., VCU Medical Ctr, Richmond, Virginia, United States
- Krieg, Richard, VCU, Richmond, Virginia, United States
- Gehr, Todd W., Virginia Commonwealth University, Fredericksburg, Virginia, United States
- Ghosh, Shobha, VCU, Richmond, Virginia, United States
Background
Intestine and gut microbiota play a major role in various diseases including diabetic nephropathy. Changes in gut microbiota influences glucagon like peptide (GLP-1) secretion. Drugs that modulate GLP-1 has been known to ameliorate not only diabetes but also improve renal function. Butyrate commonly secreted by commensal bacteria has be shown to stimulate GLP-1 release. We hypothesized that sodium butyrate (BU) might improve diabetes and renal function in animals with renal failure.
Methods
5/6 nephrectomy was done in ten Sprague dawley rats to induce RF and divided into 2 groups, untreated (RF) and butyrate treated (RF+BU). Na Butyrate (250 mg/100ml) was given in drinking water for 6 weeks. Oral Glucose tolerance test GTT and insulin tolerance test (ITT) were done by oral 2 g/kg glucose and pyruvate tolerance test (PTT) were done by giving sodium pyruvate (1.5 g/Kg) ip. Tail blood glucose was measured by at baseline and at 15, 30, 60, and 120 mins after administration to measure area under the curve (AUC). Duodenal AMPK and colon calmodulin-dependent protein kinase II (CAMKII) were measured by western blots
Results
Results in the table show that both renal failure and diabetes were ameliorated by butyrate. AMPK and CAMKII play a major role in the secretion of GLP-1. Both proteins are downregulated in RF and were restored by butyrate.
Conclusion
In a recent study it has been shown that metformin activates duodenal AMPK dependent pathway to lower hepatic glucose production. PTT, a measure hepato- gluconeogenesis suggests that butyrate may act by similar mechanism. In addition recent clinical trials have shown GLP- 1 agonist improves GFR in renal failure. By improving GLP-1 secretion butyrate may improve diabetes and renal function in renal failure.
| Control | RF | RF+BU | |
| Creatinine (mg/dl) | 0.42±0.1 | 0.93±0.2* | 0.63±0.2# |
| Urinary protein/creatinine | 138.5±2.2 | 241.5±31.4* | 154.9±26.6# |
| GTT AUC (mg.min/dl) | 18735±943 | 29954±7577* | 18590±1242# |
| PTT AUC (mg.min/dl) | 16770±683 | 21950±665* | 18123±1348# |
| ITT (AUC) (mg.min/dl) | 12558±919 | 16633±698* | 12555±812# |
| Plasma GLP (pg/ml) | 219.5±25.4 | 151.9±19.1* | 222.5±15.4# |
| pAMPK/AMPK Duodenum (Fold Change) | 1.0±0.2 | 0.49±0.06* | 0.89±0.26# |
| Calmodulin Kinase II (CamkII) Fold change | 1.0±0.2 | 0.42±0.06* | 0.74±0.09# |
*P<0.05 compared to control; #p<0.05 compared to RF