The impact of triglycerides on glucose tolerance: Lipotoxicity revisited

Seghieri, Marta; Tricò, Domenico; Natali, Andrea

doi:10.1016/j.diabet.2017.04.010

Cited by 40 publications

(31 citation statements)

References 92 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In this view, gaining a deeper knowledge of the signals by which β-cells can be stimulated to release insulin would be clinically relevant. In agreement with previous observations [4–6], in this study we found that adolescents with high fasting TG have 34% higher fasting insulin levels and 35% higher ISR than subjects with normal TG, despite similar insulin sensitivity and insulin clearance (Table 1). This translated into a much higher basal insulin daily output (139 [179–107] vs 101 [70–142] U/24h, p <0.0001).…”

Section: Discussionsupporting

confidence: 93%

“…Preliminary evidence suggests a primary role for plasma triglycerides (TG) in directly enhancing β-cell function. In fact, although chronic exposure to high TG may lead to β-cell dysfunction, 4 an overnight infusion of lipids was able to markedly increase fasting insulin secretion in young people, 5 and endogenous TG were directly associated with both fasting and glucose-stimulated insulin secretion in a large cohort of non-diabetic adults (n = 1016). 6 Endogenous TG are transported from liver to peripheral tissues in the core of very low-density lipoproteins (VLDL), whose size closely reflects their TG content.…”

Section: Introductionmentioning

confidence: 99%

“…In fact, although chronic exposure to high TG may lead to β-cell dysfunction [4], an overnight infusion of lipids was able to markedly increase fasting insulin secretion in youths [5], and endogenous TG were directly associated with both fasting and glucose-stimulated insulin secretion in a large cohort of non-diabetic adults ( n =1,016) [6]. …”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Triglyceride‐rich very low‐density lipoproteins (VLDL) are independently associated with insulin secretion in a multiethnic cohort of adolescents

Tricò

Natali

Mari

et al. 2018

Diabetes Obesity Metabolism

View full text Add to dashboard Cite

Excess insulin secretion and hyperinsulinaemia contribute to the progression of type 2 diabetes. However, the mechanisms leading to insulin hypersecretion remain largely unknown. Based on our preliminary data, we examined whether triglycerides and very low-density lipoprotein (VLDL) are independently associated with insulin secretion, and whether ethnicity/race modulates these associations. Fasting triglycerides and VLDL were measured in a multiethnic cohort of 630 non-diabetic adolescents. Insulin secretion, β-cell function parameters, insulin sensitivity and insulin clearance were estimated through a 3-h oral glucose tolerance test. Metabolic assessments were repeated after 2 years in 239 subjects. Triglycerides and triglyceride-rich VLDL (large and medium size fractions) were associated with both basal and glucose-stimulated insulin secretion, after adjustment for age, sex, ethnicity, BMI z-score, plasma glucose, and insulin sensitivity. Ethnicity per se had an impact on lipid profile and β-cell function, but did not modulate the effect of triglycerides/VLDL on insulin secretion. At follow-up, changes in triglyceride levels were proportional to changes in insulin secretion. These findings support the hypothesis that hypertriglyceridaemia is an important stimulus for β-cell insulin release in young people under both fasting and fed conditions.

show abstract

Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Triglyceride‐rich very low‐density lipoproteins (VLDL) are independently associated with insulin secretion in a multiethnic cohort of adolescents

Tricò

Natali

Mari

et al. 2018

Diabetes Obesity Metabolism

View full text Add to dashboard Cite

show abstract

“…Plasma NEFA concentrations are higher in obese individuals [1] and this may contribute to the pathogenesis of obesityassociated insulin resistance and beta cell dysfunction [2][3][4][5]. However, the distinct and potentially opposite effects of individual NEFA on insulin action and secretion are still poorly understood.…”

Section: Introductionmentioning

confidence: 99%

Circulating palmitoleic acid is an independent determinant of insulin sensitivity, beta cell function and glucose tolerance in non-diabetic individuals: a longitudinal analysis

et al. 2019

View full text Add to dashboard Cite

Aims/hypothesis Experimental studies suggest that the fatty acid palmitoleate may act as an adipocyte-derived lipid hormone (or 'lipokine') to regulate systemic metabolism. We investigated the relationship of circulating palmitoleate with insulin sensitivity, beta cell function and glucose tolerance in humans. Methods Plasma NEFA concentration and composition were determined in non-diabetic individuals from the Relationship between Insulin Sensitivity and Cardiovascular disease (RISC) study cohort at baseline (n = 1234) and after a 3 year follow-up (n = 924). Glucose tolerance, insulin secretion and beta cell function were assessed during an OGTT. Whole-body insulin sensitivity was measured by a hyperinsulinaemic-euglycaemic clamp (M/I) and OGTT (oral glucose insulin sensitivity index [OGIS]). The liver insulin resistance index was calculated using clinical and biochemical data. Body composition including fat mass was determined by bioelectrical impedance. Results Circulating palmitoleate was proportional to fat mass (r = 0.21, p < 0.0001) and total NEFA levels (r = 0.19, p < 0.0001). It correlated with whole-body insulin sensitivity (M/I: standardised regression coefficient [std. β] = 0.16, p < 0.0001), liver insulin resistance (std. β = −0.14, p < 0.0001), beta cell function (potentiation: std. β = 0.08, p = 0.045) and glucose tolerance (2 h glucose: std. β = −0.24, p < 0.0001) after adjustment for age, sex, BMI, adiposity and other NEFA. High palmitoleate concentrations prevented the decrease in insulin sensitivity associated with excess palmitate (p = 0.0001). In a longitudinal analysis, a positive independent relationship was observed between changes in palmitoleate and insulin sensitivity over time (std. β = 0.07, p = 0.04). Conclusions/interpretation We demonstrated that plasma palmitoleate is an independent determinant of insulin sensitivity, beta cell function and glucose tolerance in non-diabetic individuals. These results support the role of palmitoleate as a beneficial lipokine released by adipose tissue to prevent the negative effects of adiposity and excess NEFA on systemic glucose metabolism.

show abstract

“…Overall, excess fatty acids accompanied by the accumu lation of TG results in chronic cellular injury, which is now termed as lipotoxicity 9) . TGs are toxic due to the presence of nonesterified fatty acids (NEFAs) and increase in their products due to the failure of esterification of the TGs 10) . NEFAinduced mitochondrial dysfunction plays an im portant role in the impairment of pancreatic βcells and skeletal myocytes.…”

Section: Discussionmentioning

confidence: 99%

Acute Tubular Necrosis associated with the Ketogenic Diet in a Child with Intractable Epilepsy

Yoo

Yim

2019

Child Kidney Dis

View full text Add to dashboard Cite

The ketogenic diet (KD) has been used as an effective antiepileptic therapy for intractable childhood epilepsy. However, various adverse effects have been reported with use of the KD. We report a case of a child who developed acute tubular necrosis subsequent to therapy with KD. A 5-year-old girl had myoclonic epilepsy with developmental delay. She was under the treatment with antiepileptic drugs since the age of 3 months and on the KD during the past 18 months. Proteinuria persisted intermittently with the initiation of the KD and subsequently increased in the past 2 months. She was admitted with intermittent mild fever, vomiting, and lethargy for the past 3-4 weeks. At the time of admission, she presented with hypertriglyceridemia, heavy proteinuria, renal Fanconi syndrome, and acute kidney injury. Renal sonography showed a marked increase in the size and parenchymal echogenicity of both kidneys. A renal biopsy revealed acute tubular necrosis accompanied by early interstitial fibrosis. After the withdrawal of the KD and supportive therapy, without changing other anticonvulsants and their dosages, improvement of renal function was observed. Proteinuria had disappeared after 1 month and kidney size returned to normal after 8 months. It is hypothesized that the KD can induce and/or aggravate the renal tubulointerstitial injury in some patients who are under the treatment with anticonvulsants.

show abstract

The impact of triglycerides on glucose tolerance: Lipotoxicity revisited

Cited by 40 publications

References 92 publications

Triglyceride‐rich very low‐density lipoproteins (VLDL) are independently associated with insulin secretion in a multiethnic cohort of adolescents

Triglyceride‐rich very low‐density lipoproteins (VLDL) are independently associated with insulin secretion in a multiethnic cohort of adolescents

Circulating palmitoleic acid is an independent determinant of insulin sensitivity, beta cell function and glucose tolerance in non-diabetic individuals: a longitudinal analysis

Acute Tubular Necrosis associated with the Ketogenic Diet in a Child with Intractable Epilepsy

Contact Info

Product

Resources

About