Insulin resistance in pathogenesis of type 2 diabetes mellitus

This review focuses on the mechanisms of impaired sensitivity to insulin associated withevolution of carbohydrate metabolism disorders from enhanced fasting glycemia (EFG) to impaired glucose tolerance (IGT) and type 2 diabetes.Disturbances of glucose utilization at the receptor and post-receptor levels are considered along with the role of glucose and lipotoxicity. Original dataon insulin resistance (IR) in patients with disorders of carbohydrate metabolism are presented. Insulin sensitivity in DM2, EFG and IGT is shownto be 50, 25 and 15% lower respectively than in normal subjects. M-index positively correlates with BMI and quality of metabolic control (HbA1cand triglyceride levels). The differences in clinical and biochemical characteristics of DM2 patients are analysed depending on the degree of IR.Adiponectin and resistin levels in DM2 are shown to be lower than in healthy subjects while TNF-a and proinsulin levels increase. Therapy withmetformin, pyoglitazone, and insulin improves insulin sensitivity even in patients with early disturbances of carbohydrate metabolism. It is concludedthat intensive hypoglycemic therapy should be initiated before marked deterioration of insulin sensitivity developed.

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Role of nutrition in preventing insulin resistance in children

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem-2015-0189 ◽

2016 ◽

Vol 29 (3) ◽

Cited By ~ 3

Author(s):

Annalisa Blasetti ◽

Simone Franchini ◽

Laura Comegna ◽

Giovanni Prezioso ◽

Francesco Chiarelli

Keyword(s):

Insulin Resistance ◽

Insulin Sensitivity ◽

Fetal Development ◽

Maternal Nutrition ◽

Dietary Habits ◽

Prenatal Period ◽

Dietary Carbohydrates ◽

Macro And Micronutrients

AbstractNutrition during prenatal, early postnatal and pubertal period is crucial for the development of insulin resistance and its consequences. During prenatal period fetal environment and nutrition seems to interfere with metabolism programming later in life. The type of dietary carbohydrates, glycemic index, protein, fat and micronutrient content in maternal nutrition could influence insulin sensitivity in the newborn. The effects of lactation on metabolism and nutritional behavior later in life have been studied. Dietary habits and quality of diet during puberty could prevent the onset of a pathological insulin resistance through an adequate distribution of macro- and micronutrients, a diet rich in fibers and vegetables and poor in saturated fats, proteins and sugars. We want to overview the latest evidences on the risk of insulin resistance later in life due to both nutritional behaviors and components during the aforementioned periods of life, following a chronological outline from fetal development to adolescence.

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Influence of insulin resistance on the course of ischemic stroke in the acute period

Practical medicine ◽

10.32000/2072-1757-2020-5-93-98 ◽

2020 ◽

Vol 18 (5) ◽

pp. 93-98

Author(s):

L. B. NOVIKOVA ◽

◽

G. I. IZHBULDINA ◽

Keyword(s):

Insulin Resistance ◽

Ischemic Stroke ◽

Clinical Outcome ◽

Carbohydrate Metabolism ◽

Neurological Deficit ◽

Glucose Metabolism Disorders ◽

C Peptide ◽

Acute Period

Among the reasons that increase the risk of stroke, its severity and outcome, a special place is given to disorders of carbohydrate metabolism. However, to date, there is no consensus on the role of hyperglycemia in stroke, whether it is physiological or pathological. The purpose to study the effect of insulin resistance on the course and clinical outcome of ischemic stroke (IS) in the acute period. Material and methods. A total of 862 patients with IS (370 men, 492 women), mean age was 66,1 ± 10,8 years. The degree of neurological deficit (NIHSS scale) and clinical outcome were assessed. When admitted to hospital, the level of glycemia, insulin, and C-peptide in the fasting blood were found. Results. In 186 (21,6%) patients type 2 diabetes mellitus (DM) was diagnosed. In 27,8% of patients without DM and 76,3% of patients with DM hyperglycemia was detected. In patients without DM with hyperglycemia, compared with patients with normoglycemia, a higher representation of severe neurological deficit (by 14,7%), a lower frequency of noticeable positive dynamics (by 14,8%), and a higher mortality rate (by 11,5%) were found. In patients with DM, hyperglycemia was associated with a lower incidence of noticeable positive dynamics (by 27,7%). The development of IS is accompanied by an increase in the blood level of C-peptide more than twice. High values of the C-peptide/insulin ratio are associated with a higher frequency of severe neurological deficit in patients with DM (by 32,4%) and without DM (by 23,8%), and a decrease in the incidence of noticeable positive dynamics (by 23,5% and 20,9%, respectively). Conclusion. Development of IS is characterized by high representation of disorders of carbohydrate metabolism. The severity of glucose metabolism disorders is interrelated with the severity and clinical outcome of the disease.

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Adipocyte PU.1 knockout promotes insulin sensitivity in HFD-fed obese mice

Scientific Reports ◽

10.1038/s41598-019-51196-8 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 1

Author(s):

Denise E. Lackey ◽

Felipe C. G. Reis ◽

Roi Isaac ◽

Rizaldy C. Zapata ◽

Dalila El Ouarrat ◽

...

Keyword(s):

Gene Expression ◽

Insulin Resistance ◽

Type 2 Diabetes ◽

Insulin Sensitivity ◽

Glucose Tolerance ◽

Target Genes ◽

Obese Mice ◽

Tissue Macrophage

Abstract Insulin resistance is a key feature of obesity and type 2 diabetes. PU.1 is a master transcription factor predominantly expressed in macrophages but after HFD feeding PU.1 expression is also significantly increased in adipocytes. We generated adipocyte specific PU.1 knockout mice using adiponectin cre to investigate the role of PU.1 in adipocyte biology, insulin and glucose homeostasis. In HFD-fed obese mice systemic glucose tolerance and insulin sensitivity were improved in PU.1 AKO mice and clamp studies indicated improvements in both adipose and liver insulin sensitivity. At the level of adipose tissue, macrophage infiltration and inflammation was decreased and glucose uptake was increased in PU.1 AKO mice compared with controls. While PU.1 deletion in adipocytes did not affect the gene expression of PPARg itself, we observed increased expression of PPARg target genes in eWAT from HFD fed PU.1 AKO mice compared with controls. Furthermore, we observed decreased phosphorylation at serine 273 in PU.1 AKO mice compared with fl/fl controls, indicating that PPARg is more active when PU.1 expression is reduced in adipocytes. Therefore, in obesity the increased expression of PU.1 in adipocytes modifies the adipocyte PPARg cistrome resulting in impaired glucose tolerance and insulin sensitivity.

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The Role of Diet on Insulin Sensitivity

Nutrients ◽

10.3390/nu12103042 ◽

2020 ◽

Vol 12 (10) ◽

pp. 3042

Author(s):

Maria Mirabelli ◽

Diego Russo ◽

Antonio Brunetti

Keyword(s):

Insulin Resistance ◽

Type 2 Diabetes ◽

Cardiovascular Disease ◽

Insulin Sensitivity ◽

Dietary Composition ◽

Reproductive Disorders

Growing evidence shows that dietary composition has a marked impact on the risk of developing obesity, type 2 diabetes (T2D), cardiovascular disease (CVD), certain types of endocrine cancer and many other intertwined metabolic and reproductive disorders, all featured by insulin resistance (IR) [...]

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Effect of age and moderate food restriction on insulin sensitivity in Wistar rats: role of adiposity

Journal of Endocrinology ◽

10.1677/joe.1.07043 ◽

2007 ◽

Vol 194 (1) ◽

pp. 131-141 ◽

Cited By ~ 88

Author(s):

Fernando Escrivá ◽

M Lucía Gavete ◽

Yasmín Fermín ◽

Coralia Pérez ◽

Nilda Gallardo ◽

...

Keyword(s):

Insulin Resistance ◽

Insulin Sensitivity ◽

Calorie Restriction ◽

Food Restriction ◽

Glucose Utilization ◽

Oral Glucose ◽

Old Rats ◽

Total Fat ◽

Total Body

Insulin resistance develops with ageing in humans and rodents. Here, we have studied the evolution of insulin sensitivity with ageing trying to discriminate the role of adiposity from that of ageing in this process. We performed oral glucose tolerance tests and determined overall and tissue-specific glucose utilization under euglycemic-hyper-insulinemic conditions in 3-, 8-, and 24-month-old rats fed ad libitum, and in 8- and 24-month-old rats after 3 months of calorie restriction. Body composition and adipocyte-derived cytokines such as leptin, resistin, and adiponectin were analyzed. Overall insulin sensitivity decreases with ageing. Calorie restriction improves global insulin sensitivity in 8- but not in 24-month-old rats. Insulin-stimulated glucose utilization in adipose tissues decreases in 8 months, while in oxidative muscles it reaches significance only in older rats. Calorie restriction restores adipose tissue insulin sensitivity only in 8-month-old rats and no changes are observed in muscles of 24-month-old rats. Resistin and leptin increase with ageing. Food restriction lowers resistin and increases adiponectin in 8-month-old rats and decreases leptin in both ages. Visceral and total fat increase with ageing and decrease after calorie restriction. We conclude that accretion of visceral fat plays a key role in the development of insulin resistance after sexual maturity, which is reversible by calorie restriction. With aging, accumulation of retroperitoneal and total body fat leads to impaired muscle glucose uptake and to a state of insulin resistance that is difficult to reverse.

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Association between Dietary Pattern and Insulin Resistance

Journal of Pharmaceutical Research International ◽

10.9734/jpri/2021/v33i33a31769 ◽

2021 ◽

pp. 39-45

Author(s):

Manal Murad ◽

Abdullah Al Alhareth ◽

Mohammed Alnassir ◽

Haifa Alkheledan ◽

Arafah Alsayed ◽

...

Keyword(s):

Insulin Resistance ◽

Hormone Sensitive Lipase ◽

Current Evidence ◽

Potential Association ◽

Enhance Insulin Sensitivity ◽

Hormone Sensitive ◽

High Protein Diets

The current evidence supports the fact that obesity is directly involved in a significant correlation with insulin resistance and type 2 diabetes mellitus (T2DM). Many studies have been published to report the role of many micronutrients, including carbohydrate, lipids and proteins which enhance or worsen the sensitivity of insulin. Thus, this literature review aims to assess the potential association between the different dietary components and insulin resistance based on the findings from the current studies in the literature. It has been suggested that replacing the consumption of fructose with other carbohydrates substances as fibers and starch might reduce such events and enhance insulin sensitivity as these substances pass intact through the gastrointestinal tract to the colon where they begin to be fermented. Additionally, carbohydrates substances reduce the utilization of free fatty acids by enhancing G-coupling through inhibition of the hormone-sensitive lipase, while the effect of overconsumption of glucose and fructose on insulin resistance is still controversial. Moreover, the quality of lipids is far more important than the quantity. Therefore, frequent ingestion of vegetable oils is suggested to enhance the sensitivity. As for proteins, high protein diets have been proposed for their useful effects. However, they should be carefully described to avoid their potential adverse events.

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SAT-653 Exploring the Role of Brown Adipokines on Hepatic Insulin Resistance Using a Microfluidic Organ-On-Chip

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa046.570 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

Author(s):

Nida Tanataweethum ◽

Chaeeun Lee ◽

Allyson Trang ◽

Franklin Zhong ◽

Kihwan Kim ◽

...

Keyword(s):

Insulin Resistance ◽

Type 2 Diabetes ◽

Insulin Sensitivity ◽

Glucose Production ◽

Conditioned Media ◽

Hepatic Insulin Resistance ◽

Brown Adipocyte ◽

On Chip

Abstract The development of insulin resistance (IR) in liver is a key of pathophysiologic response in type 2 diabetes. Although insulin resistance impairs its ability to suppress hepatic glucose production, insulin regulation of lipogenesis is maintained (1). Currently available insulin sensitizers are effective at lowering glucose levels, but have significant adverse effect on weight gain due to triglyceride accumulation, which highlights a need to develop new therapeutic treatment options for type 2 diabetes. Brown adipose tissue (BAT) has been studied as a new target for anti-obesity and type 2 diabetes as BAT stimulation increases energy expenditure, reduces adiposity, and improves insulin sensitivity (2). However, the underlying mechanisms are not completely understood. To identify the role of BAT adipokines on hepatic insulin resistance, we developed an insulin resistant liver organ-on-chip model and then perfused primary mouse brown adipocyte conditioned media through the hepatocytes. Our results demonstrate that IR hepatocytes treated with brown adipocyte - conditioned media restores insulin sensitivity and improves glucose metabolism. This was verified by significantly increased expression of Phospho-Akt (Ser473) and glucose production gene markers (G6pc and PEPCK), lowered glucose production, increased glucose uptake, and increased glycogen synthesis in treated hepatocytes over IR group (p < 0.05). Our results also indicate that brown adipocyte - conditioned media treatment has the potential to suppress lipogenesis in hepatic insulin resistance. This was confirmed by significantly reduced expression of a lipogenesis gene marker (SREPB1) and fatty acid uptake in treated hepatocytes over IR group (p < 0.05). Current efforts are focused towards identifying the BAT adipokine via mass spectrometry. We conclude that BAT-derived endocrine factors could be a potential target for new drug discovery for obesity and type 2 diabetes treatment. Reference: (1) Langlet et al. Cell. 2017 Nov;171(4):824-835. (2) Subhadraw et al. Am J Physiol Endocrinol Metlab. 2015 Jun;308(12):E1043-E1055. Nothing to Disclose: NT, CL, AT, FZ, KK, JM, RC, AB

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