Abnormalities in insulin secretion in type 2 diabetes mellitus

Guillausseau, P. J.; Méas, T.; Virally, Marie; Laloi-Michelin, M.; Médeau, V.; Kévorkian, Jean-Philippe

doi:10.1016/s1262-3636(08)73394-9

Cited by 158 publications

(106 citation statements)

References 62 publications

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“…1,3 Data suggest that an impaired first phase of insulin secretion is an indicator of beta cell dysfunction encountered in patients with early diabetes and prediabetes. 1,2,[4][5][6] The effect of insulin on glucose homeostasis is to reduce the postprandial glucose levels, a goal that is achieved via three actions. a) It increases the glucose uptake by peripheral tissues, mainly by skeletal muscles.…”

Section: (Figure 1)mentioning

confidence: 99%

Postprandial dysmetabolism: Too early or too late?

Pappas¹,

Kandaraki²,

Tsirona³

et al. 2016

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postprandial dysmetabolism is a postprandial state characterized by abnormal metabolism of glucose and lipids and, more specifically, of elevated levels of glucose and triglyceride (Tg) containing lipoproteins. Since there is evidence that postprandial dysmetabolism is associated with increased cardiovascular mortality and morbidity, due to macro-and microvascular complications, as well as with conditions such as polycystic ovary syndrome (pCOS) and nonalcoholic fatty liver disease (NaFlD), it is recommended that clinicians be alert for early detection and management of this condition. management consists of a holistic approach including dietary modification, exercise and use of hypoglycemic and hypolipidemic medication aiming to decrease the postprandial values of circulating glucose and triglycerides. This review aims to explain glucose and lipid homeostasis and the impact of postprandial dysmetabolism on the cardiovascular system as well as to offer suggestions with regard to the therapeutic approach for this entity. however, more trials are required to prevent or reverse early and not too late the actual tissue damage due to postprandial dysmetabolism.

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Section: (Figure 1)mentioning

confidence: 99%

Postprandial dysmetabolism: Too early or too late?

Pappas¹,

Kandaraki²,

Tsirona³

et al. 2016

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“…Insulin pathophysiology has two components: one is functional and arises from abnormal insulin secretion kinetics and reduced insulin sensitivity and the other is manifestly pathological in the sense that there is a quantifiable diminution in pancreatic b-cell mass with heightened apoptotic activity (Guillausseau et al 2008). A genetic component to type 2 diabetes risk is now well recognized (Zeggini & McCarthy 2007).…”

Section: Hyperinsulinemiamentioning

confidence: 99%

The cellular and molecular mechanisms by which insulin influences breast cancer risk and progression

Rose

Vona-Davis

2012

Endocrine-Related Cancer

138

125

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Epidemiological studies have related hyperinsulinemia and type 2 diabetes to an increased breast cancer risk, an aggressive and metastatic phenotype, and a poor prognosis. Furthermore, diabetic retinopathy arises from pathological angiogenesis, which is also essential for breast cancer growth and metastasis. Insulin stimulates the proliferation of some human breast cancer cell lines in vitro by mechanisms that use both the phosphatidylinositol-3 kinase and the mitogen-activated protein kinase/Akt signaling pathways; it is also a cell survival (anti-apoptotic) agent and enhances tumor cell migration and invasive capacity. Hyperinsulinemia affects breast cancer cells via the endocrine system, but experimental studies suggest the importance of paracrine mechanisms operating by the effects of insulin on the secretion of adipokines from tumor-associated adipose tissue. In such a system, one adipokine, leptin, has stimulatory paracrine effects on breast cancer cell proliferation and survival, while a second, adiponectin, is inhibitory. Leptin, vascular endothelial growth factor, another insulin-regulated adipokine, and insulin itself also stimulate angiogenesis. Insulin has complex interactions with estrogens: it induces adipose stromal cell aromatase and tumor cell sex steroid hormone receptor expression and suppresses sex hormonebinding globulin, which may enhance estrogen synthesis and bioactivity with consequent promotion of estrogen-dependent breast cancer. All these actions influence the later steps in breast cancer development but genetic studies are also revealing connections between gene abnormalities related to type 2 diabetes and the initiation stage of breast carcinogenesis. Understanding the various mechanisms by which insulin participates in breast cancer cell biology provides opportunities for novel approaches to treatment.

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“…Type 2 diabetes is a multifaceted disease, marked by decreased glucose peripheral uptake, increased hepatic glucose production, and decreased insulin secretion and reduced insulin sensitivity (1). Insulin resistance, defined as a diminished ability of cells, such as adipocytes, skeletal muscle cells, and hepatocytes, to respond to the action of insulin, plays a central role in the development of several metabolic abnormalities and diseases, such as obesity, type 2 diabetes, and the metabolic syndrome (2,3).…”

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confidence: 99%

The Effects of Palmitate on Hepatic Insulin Resistance Are Mediated by NADPH Oxidase 3-derived Reactive Oxygen Species through JNK and p38MAPK Pathways

Gao

Nong

Huang

et al. 2010

Journal of Biological Chemistry

288

229

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Elevated plasma free fatty acid (FFA) levels in obesity may play a pathogenic role in the development of insulin resistance. However, molecular mechanisms linking FFA to insulin resistance remain poorly understood. Oxidative stress acts as a link between FFA and hepatic insulin resistance. NADPH oxidase 3 (NOX3)-derived reactive oxygen species (ROS) may mediate the effect of TNF-␣ on hepatocytes, in particular the drop in cellular glycogen content. In the present study, we define the critical role of NOX3-derived ROS in insulin resistance in db/db mice and HepG2 cells treated with palmitate. The db/db mice displayed increased serum FFA levels, excess generation of ROS, and upregulation of NOX3 expression, accompanied by increased lipid accumulation and impaired glycogen content in the liver. Similar results were obtained from palmitate-treated HepG2 cells. The exposure of palmitate elevated ROS production and NOX3 expression and, in turn, increased gluconeogenesis and reduced glycogen content in HepG2 cells. We found that palmitate induced hepatic insulin resistance through JNK and p38 MAPK pathways, which are rescued by siRNA-mediated NOX3 reduction. In conclusion, our data demonstrate a critical role of NOX3-derived ROS in palmitate-induced insulin resistance in hepatocytes, indicating that NOX3 is the predominant source of palmitate-induced ROS generation and that NOX3-derived ROS may drive palmitate-induced hepatic insulin resistance through JNK and p38 MAPK pathways.

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Abnormalities in insulin secretion in type 2 diabetes mellitus

Cited by 158 publications

References 62 publications

Postprandial dysmetabolism: Too early or too late?

Postprandial dysmetabolism: Too early or too late?

The cellular and molecular mechanisms by which insulin influences breast cancer risk and progression

The Effects of Palmitate on Hepatic Insulin Resistance Are Mediated by NADPH Oxidase 3-derived Reactive Oxygen Species through JNK and p38MAPK Pathways

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