Impaired Insulin Secretion in Four Tangier Disease Patients with ABCA1 Mutations

Koseki, Masahiro; Matsuyama, Akifumi; Nakatani, Kazuhiro; Inagaki, Miwako; Nakaoka, Hajime; Kawase, Ryota; Yuasa-Kawase, Miyako; Tsubakio-Yamamoto, Kazumi; Masuda, Daisuke; Sandoval, Jose C.; Ohama, Tohru; Nakagawa-Toyama, Yumiko; Matsuura, Fumihiko; Nishida, Makoto; Ishigami, Masato; Hirano, Ken‐ichi; Sakane, Naoki; Kumon, Yoshitaka; Suehiro, Tadashi; Nakamura, Tadashi; Shimomura, Iichiro; Yamashita, Shizuya

doi:10.5551/jat.e599

Cited by 57 publications

(42 citation statements)

References 13 publications

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“…In fact, in a Japanese study, four subjects affected by overt Tangier disease underwent OGTT and showed progressively increased plasma glucose concentrations until the diagnosis of T2D. The calculated insulinogenic index, an index of early betacell secretion during OGTT, was significantly lower than in controls [48]. This study suggests that the impairment of ABCA1 function may be directly involved in defective insulin secretion.…”

Section: Dyslipidemia Contributing To Diabetes and Vascular Complicatmentioning

confidence: 78%

“…In this regard, the Tangier disease is an excellent model of HDL-C particle deficiency, as it is characterized by a mutation in the ABCA1 protein, which causes an impaired function, and eventually an inability of the peripheral cells to remove the excessive cholesterol. The resulting clinical picture is characterized by an increased occurrence to cardiovascular events in these patients and, surprisingly, reduced insulin secretion and hyperglycemia [47,48]. In fact, in a Japanese study, four subjects affected by overt Tangier disease underwent OGTT and showed progressively increased plasma glucose concentrations until the diagnosis of T2D.…”

Section: Dyslipidemia Contributing To Diabetes and Vascular Complicatmentioning

confidence: 99%

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Dyslipidemia and Diabetes: Reciprocal Impact of Impaired Lipid Metabolism and Beta-Cell Dysfunction on Micro- and Macrovascular Complications

Rotella²,

2012

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■ AbstractPatients with diabetes frequently exhibit the combined occurrence of hyperglycemia and dyslipidemia. Published data on their coexistence are often controversial. Some studies provide evidence for suboptimal lifestyle and exogenous hyperinsulinism at "mild insulin resistance" in adult diabetic patients as main pathogenic factors. In contrast, other studies confirm that visceral adiposity and insulin resistance are the basic features of dyslipidemia in type 2 diabetes (T2D). The consequence is an excess of free fatty acids, which causes hepatic gluconeogenesis to increase, metabolism in muscles to shift from glucose to lipid, beta-cell lipotoxicity, and an appearance of the classical "lipid triad", without real hypercholesterolemia. Recently, it has been proposed that cholesterol homeostasis is important for an adequate insulin secretory performance of beta-cells. The accumulation of cholesterol in beta-cells, caused by defective high-density lipoprotein (HDL) cholesterol with reduced cholesterol efflux, induces hyperglycemia, impaired insulin secretion, and beta-cell apoptosis. Data from animal models and humans, including humans with Tangier disease, who are characterized by very low HDL cholesterol levels, are frequently associated with hyperglycemia and T2D. Thus, there is a reciprocal influence of dyslipidemia on beta-cell function and inversely of beta-cell dysfunction on lipid metabolism and micro-and macrovascular complications. It remains to be clarified how these different but mutually influencing adverse effects act in together to define measures for a more effective prevention and treatment of micro-and macrovascular complications in diabetes patients. While the control of circulating low-density lipoprotein (LDL) cholesterol and the level of HDL cholesterol are determinant targets for the reduction of cardiovascular risk, based on recent data, these targets should also be considered for the prevention of betacell dysfunction and the development of type 2 diabetes. In this review, we analyze consolidated data and recent advances on the relationship between lipid metabolism and diabetes mellitus, with particular attention to the reciprocal effects of the two features of the disease and the development of vascular complications.

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Section: Dyslipidemia Contributing To Diabetes and Vascular Complicatmentioning

confidence: 78%

Section: Dyslipidemia Contributing To Diabetes and Vascular Complicatmentioning

confidence: 99%

Dyslipidemia and Diabetes: Reciprocal Impact of Impaired Lipid Metabolism and Beta-Cell Dysfunction on Micro- and Macrovascular Complications

Rotella²,

2012

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“…HDL also reversed the toxic effects of oxidized LDL on beta cells that are associated with apoptosis and cJNK mediated transcriptional repression of the insulin gene caused cJNK mediated (Abderrahmani et al, 2007). Oral glucose tolerance test in a limited number of patients with Tangier disease (that lack or have dysfunctional ABCA1) showed that they had glucose intolerance as compared to controls (Koseki et al, 2009), thus implicating ABCA1, apoA-I and HDL in glucose metabolism. Cell culture studies using primary pancreatic islets cells and a pancreatic -cell line (Min6), showed that lipid free apoA-I or apoA-II or reconstituted HDL increased insulin secretion up to 5-fold in a Ca 2+ dependant manner (Fryirs et al, 2010).…”

Section: Effects Of Hdl On Diabetes Mellitusmentioning

confidence: 99%

“…In vivo and in vitro studies have provided evidence that HDL may have beneficial effects on glucose metabolism (Koseki et al, 2009;Rutti et al, 2009). Ex vivo studies showed that HDL and delipidated apoA-I or S1P decreased IL-1 and glucose-mediated apoptosis and thus increased the survival of human and murine islets.…”

Section: Effects Of Hdl On Diabetes Mellitusmentioning

confidence: 99%

Pleiotropic Functions of HDL Lead to Protection from Atherosclerosis and Other Diseases

Zannis¹,

Kateifides²,

Fotakis³

et al. 2012

Dyslipidemia - From Prevention to Treatment

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“…However, the human genetic data mentioned before do not unequivocally support the findings made in the genetic mouse models. On the one hand, decreased glucose-induced insulin secretion has been reported in ABCA1-deficient patients with Tangier disease or heterozygous carriers of ABCA1 mutations (Koseki et al 2009;Vergeer et al 2010). On the other hand, mutations in ABCA1 have not been associated with increased risk of diabetes (Schou et al 2012).…”

Section: Beneficial Effects Of Hdl On Insulin Secretionmentioning

confidence: 99%

HDLs, Diabetes, and Metabolic Syndrome

Vollenweider

Eckardstein

Widmann

2014

High Density Lipoproteins

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The prevalence of type 2 diabetes mellitus and of the metabolic syndrome is rising worldwide and reaching epidemic proportions. These pathologies are associated with significant morbidity and mortality, in particular with an excess of cardiovascular deaths. Type 2 diabetes mellitus and the cluster of pathologies including insulin resistance, central obesity, high blood pressure, and hypertriglyceridemia that constitute the metabolic syndrome are associated with low levels of HDL cholesterol and the presence of dysfunctional HDLs. We here review the epidemiological evidence and the potential underlying mechanisms of this association. We first discuss the well-established association of type 2 diabetes mellitus and insulin resistance with alterations of lipid metabolism and how these alterations may lead to low levels of HDL cholesterol and the occurrence of dysfunctional HDLs. We then present and discuss the evidence showing that HDL modulates insulin sensitivity, insulin-independent glucose uptake, insulin secretion, and beta cell survival. A dysfunction in these actions could play a direct role in the pathogenesis of type 2 diabetes mellitus.

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Impaired Insulin Secretion in Four Tangier Disease Patients with ABCA1 Mutations

Cited by 57 publications

References 13 publications

Dyslipidemia and Diabetes: Reciprocal Impact of Impaired Lipid Metabolism and Beta-Cell Dysfunction on Micro- and Macrovascular Complications

Dyslipidemia and Diabetes: Reciprocal Impact of Impaired Lipid Metabolism and Beta-Cell Dysfunction on Micro- and Macrovascular Complications

Pleiotropic Functions of HDL Lead to Protection from Atherosclerosis and Other Diseases

HDLs, Diabetes, and Metabolic Syndrome

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