scholarly journals Maintaining Effective Beta Cell Function in the Face of Metabolic Syndrome-Associated Glucolipotoxicity—Nutraceutical Options

Healthcare ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 3
Author(s):  
Mark F. McCarty ◽  
James J. DiNicolantonio

In people with metabolic syndrome, episodic exposure of pancreatic beta cells to elevated levels of both glucose and free fatty acids (FFAs)—or glucolipotoxicity—can induce a loss of glucose-stimulated insulin secretion (GSIS). This in turn can lead to a chronic state of glucolipotoxicity and a sustained loss of GSIS, ushering in type 2 diabetes. Loss of GSIS reflects a decline in beta cell glucokinase (GK) expression associated with decreased nuclear levels of the pancreatic and duodenal homeobox 1 (PDX1) factor that drives its transcription, along with that of Glut2 and insulin. Glucolipotoxicity-induced production of reactive oxygen species (ROS), stemming from both mitochondria and the NOX2 isoform of NADPH oxidase, drives an increase in c-Jun N-terminal kinase (JNK) activity that promotes nuclear export of PDX1, and impairs autocrine insulin signaling; the latter effect decreases PDX1 expression at the transcriptional level and up-regulates beta cell apoptosis. Conversely, the incretin hormone glucagon-like peptide-1 (GLP-1) promotes nuclear import of PDX1 via cAMP signaling. Nutraceuticals that quell an increase in beta cell ROS production, that amplify or mimic autocrine insulin signaling, or that boost GLP-1 production, should help to maintain GSIS and suppress beta cell apoptosis in the face of glucolipotoxicity, postponing or preventing onset of type 2 diabetes. Nutraceuticals with potential in this regard include the following: phycocyanobilin—an inhibitor of NOX2; agents promoting mitophagy and mitochondrial biogenesis, such as ferulic acid, lipoic acid, melatonin, berberine, and astaxanthin; myo-inositol and high-dose biotin, which promote phosphatidylinositol 3-kinase (PI3K)/Akt activation; and prebiotics/probiotics capable of boosting GLP-1 secretion. Complex supplements or functional foods providing a selection of these agents might be useful for diabetes prevention.

Author(s):  
Eva Decroli ◽  
Asman Manaf ◽  
Syafril Syahbuddin ◽  
Sarwono Waspadji ◽  
Dwisari Dillasamola

Objective: This study aimed to reveal differences in levels of survivin and Raf-1 kinase in prediabetes, controlled Type 2 diabetes mellitus (T2DM), uncontrolled T2DM, and their relationship with hemoglobin A1c (HbA1c) levels and serum triglyceride levels.Methods: This study was an observational study with a cross-sectional design. The study involved 60 people with T2DM who visited the endocrine and metabolic clinic and 30 prediabetes patients. The variables were survivin levels and Raf-1 kinase enzymes that examined using enzyme-linked immunosorbent assay techniques. HbA1c values are measured by high-performance liquid chromatography and triglyceride levels measured by enzymatic method.Results: Average levels of Raf-1 kinase were significantly higher in the prediabetes group, controlled T2DM, and uncontrolled T2DM (11.6±1.4 pg mL, 9.9±1.1 pg/mL, and 9.1±1.5 pg/mL). Survivin was significantly higher in the prediabetes group, controlled T2DM, and uncontrolled T2DM (5.4±0.4 pg mL, 5.0±0.2 pg/mL, and 4.7±0.1 pg/mL). There was no correlation between HbA1c with Raf-1 kinase levels (R=−0.215, p=0.250), but there was a correlation between HbA1c with serum survivin levels (R=−0.6, *p<0.05). There was a correlation between the levels of triglycerides with survivin but not with Raf-1 kinase (R=−0.267, *p=0.039).Conclusion: Survivin and Raf-1 kinase levels are lower in uncontrolled T2DM. This explained the role of survivin and Raf-1 kinase against enhancement of pancreatic beta-cell apoptosis in patients with T2DM.


2019 ◽  
Vol 27 (3) ◽  
pp. 217-220 ◽  
Author(s):  
D Miricescu ◽  
AMA Stanescu ◽  
H Lazarescu ◽  
A Kozma ◽  
A Totan ◽  
...  

PLoS Genetics ◽  
2013 ◽  
Vol 9 (5) ◽  
pp. e1003532 ◽  
Author(s):  
Tatiane C. Nogueira ◽  
Flavia M. Paula ◽  
Olatz Villate ◽  
Maikel L. Colli ◽  
Rodrigo F. Moura ◽  
...  

2021 ◽  
Vol 22 (10) ◽  
pp. 5303
Author(s):  
Safia Costes ◽  
Gyslaine Bertrand ◽  
Magalie A. Ravier

Type 2 diabetes (T2D) is characterized by chronic hyperglycemia secondary to the decline of functional beta-cells and is usually accompanied by a reduced sensitivity to insulin. Whereas altered beta-cell function plays a key role in T2D onset, a decreased beta-cell mass was also reported to contribute to the pathophysiology of this metabolic disease. The decreased beta-cell mass in T2D is, at least in part, attributed to beta-cell apoptosis that is triggered by diabetogenic situations such as amyloid deposits, lipotoxicity and glucotoxicity. In this review, we discussed the molecular mechanisms involved in pancreatic beta-cell apoptosis under such diabetes-prone situations. Finally, we considered the molecular signaling pathways recruited by glucagon-like peptide-1-based therapies to potentially protect beta-cells from death under diabetogenic situations.


2012 ◽  
pp. n/a-n/a ◽  
Author(s):  
Freddy Goldberg Eliaschewitz ◽  
Marcos Antonio Tambascia

Diabetologia ◽  
2007 ◽  
Vol 50 (4) ◽  
pp. 752-763 ◽  
Author(s):  
D. R. Laybutt ◽  
A. M. Preston ◽  
M. C. Åkerfeldt ◽  
J. G. Kench ◽  
A. K. Busch ◽  
...  

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