scholarly journals HDL (High-Density Lipoprotein) and ApoA-1 (Apolipoprotein A-1) Potentially Modulate Pancreatic α-Cell Glucagon Secretion

2020 ◽  
Vol 40 (12) ◽  
pp. 2941-2952
Author(s):  
Elettra Mancuso ◽  
Gaia Chiara Mannino ◽  
Anastasia Fuoco ◽  
Antonio Leo ◽  
Rita Citraro ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
High Density Lipoprotein ◽  
Cell Function ◽  
Cell Model ◽  
Density Lipoprotein ◽  
Glucagon Secretion ◽  
High Density ◽  
Apolipoprotein A ◽  
Increased Risk

Objective: Subjects with low levels of HDL (high-density lipoprotein) and ApoA-1 (apolipoprotein A-1) have increased risk to develop type 2 diabetes. HDL levels are an independent predictor of β-cell function and positively modulate it. Type 2 diabetes is characterized by defects in both β and α-cell function, but the effect of HDL and ApoA1 on α-cell function is unknown. Approach and Results: We observed a significant negative correlation ( r =−0.422, P <0.0001) between HDL levels and fasting glucagon in a cohort of 132 Italian subjects. In a multivariable regression analysis including potential confounders such as age, sex, BMI, triglycerides, total cholesterol, fasting and 2-hour postload glucose, and fasting insulin, the association between HDL and fasting glucagon remained statistically significant (β=−0.318, P =0.006). CD1 mice treated with HDL or ApoA-1 for 3 consecutive days showed a 32% ( P <0.001) and 23% ( P <0.05) reduction, respectively, in glucagon levels following insulin-induced hypoglycemia, compared with controls. Treatment of pancreatic αTC1 clone 6 cells with HDL or ApoA-1 for 24 hours resulted in a significant reduction of glucagon expression ( P <0.04) and secretion ( P <0.01) after an hypoglycemic stimulus and increased Akt (RAC-alpha serine/threonine-protein kinase) and FoxO1 (forkhead/winged helix box gene, group O-1) phosphorylation. Pretreatment with Akt inhibitor VIII, PI3K (phosphatidylinositol 3-kinase) inhibitor LY294002, and HDL receptor SCARB-1 (scavenger receptor class B type 1) inhibitor BLT-1 (block lipid transport-1) restored αTC1 cell response to low glucose levels. Conclusions: These results support the notion that HDL and ApoA-1 modulate glucagon expression and secretion by binding their cognate receptor SCARB-1, and activating the PI3K/Akt/FoxO1 signaling cascade in an in vitro α-cell model. Overall, these results raise the hypothesis that HDL and ApoA-1 may have a role in modulating glucagon secretion.

scholarly journals Dyslipidemia in Type 2 Diabetes mellitus

2017 ◽  
Vol 7 (2) ◽  
pp. 1149-1154 ◽  
Author(s):  
Subarna Dhoj Thapa ◽  
Shiva Raj K.C ◽  
Santosh Gautam ◽  
Deepika Gyawali
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
High Density Lipoprotein ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
High Density ◽  
Low Density ◽  
Increased Risk

Background: In type 2 diabetes mellitus lipid abnormalities are very common and is associated with increased risk of cardiovascular diseases.  This study was conducted to find association of type 2 diabetes and dyslipidemia.Materials and Methods: This cross-sectional study was conducted at KISTMCTH. All the necessary data of patient with type 2 diabetes in the period between December 2016 and May 2017 were studied.Results: Out of 199 patients with diabetes mellitus 30.7% had total cholesterol >200 mg/dl, 64.4% had elevated low density lipoprotein, 53.77% patient had elevated triglyceride and 64% patients had low high density lipoprotein level. Cholesterol showed significant correlation with triglyceride (P < 0.001), low density lipoprotein (P < 0.001). Triglyceride showed a significant negative correlation with high density lipoprotein (P < 0.01), while a highly significant positive correlation was observed with cholesterol and high density lipoprotein (P < 0.001).Conclusion: Diabetes is associated with high incidence of dyslipidemia with elevated level of low density lipoprotein, cholesterol and triglyceride.

scholarly journals Efficacy of low-dose rosuvastatin in patients with type 2 diabetes and hypo high-density lipoprotein cholesterolaemia

2014 ◽  
Vol 42 (2) ◽  
pp. 457-467 ◽  
Author(s):  
Takuyuki Katabami ◽  
Mariko Murakami ◽  
Suzuko Kobayashi ◽  
Tomoya Matsui ◽  
Makoto Ujihara ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
High Density Lipoprotein ◽  
Low Dose ◽  
Density Lipoprotein ◽  
High Density

Abstract 445: Phospholipid Levels Associated with Specific High-Density Lipoprotein Subfractions Predict Cardiovascular Risk in Young Adults with Type 2 Diabetes

2012 ◽  
Vol 32 (suppl_1) ◽  
Author(s):  
Scott M Gordon ◽  
Amy S Shah ◽  
L J Lu ◽  
Jingyuan Deng ◽  
Lawrence M Dolan ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Risk ◽  
High Density Lipoprotein ◽  
Density Lipoprotein ◽  
High Density ◽  
Phospholipid Content ◽  
Healthy Controls ◽  
Carotid Imt ◽  
Early Atherosclerosis

Risk for atherosclerosis is greatly increased in people who have type 2 diabetes (T2D). Because of this, the emerging epidemic of adolescent T2D holds ominous implications for premature cardiovascular disease (CVD). High density lipoprotein cholesterol (HDL-C) represents the body’s natural defense against CVD but its levels are depressed in individuals with T2D. Recent studies indicate HDL exists as distinct subspecies raising the possibility that certain species may be more cardioprotective than others. However, little is known regarding the role of HDL subspecies in T2D, especially in the adolescent population. Thus we sought to evaluate HDL subspecies and determine whether certain subspecies are associated with protection against the development of early atherosclerosis as measured by carotid intima medial thickness (IMT). Healthy controls and youth with T2D were recruited. Whole plasma was analyzed by high-resolution gel filtration chromatography to resolve HDL sized particles and lipids in each fraction were quantitated by colorimetric assay. T-tests were used to evaluate group differences and linear regression models were constructed to determine independent predictors of carotid IMT. Youth with T2D had higher BMI, total cholesterol and lower HDL-C compared to healthy controls, p<0.05. The groups did not differ in LDL-C, triglycerides or BP. Phospholipid distributions of HDL subspecies were found to be shifted in participants with T2D compared to controls (p<0.05). There was a significant inverse correlation between carotid IMT and the phospholipid content of larger HDL subfractions 22-24 (p<0.05) in youth with T2D. Linear models demonstrate HDL fraction 22 was the only independent predictor of carotid IMT while HDL-C, LDL-C, total -C and triglycerides were not significant. These data suggest an altered HDL particle subclass distribution may better predict protection against early atherosclerosis. Thus analyzing the HDL subspecies may be a more powerful approach to assessing cardiovascular risk than the currently accepted standard of HDL-C.

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