scholarly journals 3-Hydroxyisobutyrate, A Strong Marker of Insulin Resistance in Type 2 Diabetes and Obesity That Modulates White and Brown Adipocyte Metabolism

Diabetes ◽  
2020 ◽  
Vol 69 (9) ◽  
pp. 1903-1916 ◽  
Author(s):  
Mona S. Nilsen ◽  
Regine Å. Jersin ◽  
Arve Ulvik ◽  
André Madsen ◽  
Adrian McCann ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Brown Adipocyte ◽  
Diabetes And Obesity

scholarly journals MicroRNAs in Insulin Resistance and Obesity

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Michael D. Williams ◽  
Geraldine M. Mitchell
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Messenger Rna ◽  
Physiological Role ◽  
Mrna Translation ◽  
Aberrant Expression ◽  
Peripheral Tissues ◽  
Pancreatic Islets Of Langerhans ◽  
Diabetes And Obesity

MicroRNAs (miRNAs) are a class of short, single-stranded non-protein coding gene products which can regulate the gene expression through post-transcriptional inhibition of messenger RNA (mRNA) translation. They are known to be involved in many essential biological processes including development, insulin secretion, and adipocyte differentiation. miRNAs are involved in complex metabolic processes, such as energy and lipid metabolism, which have been studied in the context of diabetes and obesity. Obesity, hyperlipidemia (elevated levels of blood lipids), and insulin resistance are strongly associated with the onset of type 2 diabetes. These conditions are also associated with aberrant expression of multiple essential miRNAs in pancreatic islets of Langerhans and peripheral tissues, including adipose tissue. A thorough understanding of the physiological role these miRNAs play in these tissues, and changes to their expression under pathological conditions, will allow researchers to develop new therapeutics with the potential to correct the aberrant expression of miRNAs in type 2 diabetes and obesity.

scholarly journals Vitamin D 3, osteoprotegerin and other hormonal and metabolic parameters in female patients with type 2 diabetes

2012 ◽  
Vol 9 (4) ◽  
pp. 23-27 ◽  
Author(s):  
A F Verbovoi ◽  
L A Sharonova ◽  
A V Kapishnikov ◽  
D V Demidova
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Vitamin D ◽  
Vitamin D3 ◽  
Metabolic Parameters ◽  
Female Patients ◽  
Vitamin D 3 ◽  
Diabetes And Obesity

The article presents the results of evaluation of vitamin D3, osteoprotegerin, carbohydrate and fat metabolic parameters in women with type 2 diabetes and obesity. The study subjects showed an increase of osteoprotegerin, decrease of vitamin D3, insulin resistance and compensatory hyperinsulinemia.

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

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

scholarly journals Role of GALNT2 on Insulin Sensitivity, Lipid Metabolism and Fat Homeostasis

2022 ◽  
Vol 23 (2) ◽  
pp. 929
Author(s):  
Alessandra Antonucci ◽  
Antonella Marucci ◽  
Vincenzo Trischitta ◽  
Rosa Di Paola
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Common Ground ◽  
Metabolic Diseases ◽  
Atherogenic Dyslipidemia ◽  
Physiological Processes ◽  
Protein Functions ◽  
Heavy Burden ◽  
Diabetes And Obesity

O-linked glycosylation, the greatest form of post-translational modifications, plays a key role in regulating the majority of physiological processes. It is, therefore, not surprising that abnormal O-linked glycosylation has been related to several human diseases. Recently, GALNT2, which encodes the GalNAc-transferase 2 involved in the first step of O-linked glycosylation, has attracted great attention as a possible player in many highly prevalent human metabolic diseases, including atherogenic dyslipidemia, type 2 diabetes and obesity, all clustered on the common ground of insulin resistance. Data available both in human and animal models point to GALNT2 as a molecule that shapes the risk of the aforementioned abnormalities affecting diverse protein functions, which eventually cause clinically distinct phenotypes (a typical example of pleiotropism). Pathways linking GALNT2 to dyslipidemia and insulin resistance have been partly identified, while those for type 2 diabetes and obesity are yet to be understood. Here, we will provide a brief overview on the present knowledge on GALNT2 function and dysfunction and propose novel insights on the complex pathogenesis of the aforementioned metabolic diseases, which all impose a heavy burden for patients, their families and the entire society.

scholarly journals 3-Hydroxyisobutyrate, a strong marker of insulin resistance in type 2 diabetes and obesity that modulates white and brown adipocyte metabolism

2020 ◽  
Author(s):  
Ada Admin ◽  
Mona S. Nilsen ◽  
Regine Å. Jersin ◽  
Arve Ulvik ◽  
André Madsen ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Cell Types ◽  
Fatty Acid Uptake ◽  
Brown Adipocyte ◽  
Acid Uptake ◽  
Dependent Manner ◽  
Brown Adipocytes ◽  
Branched Chain

Circulating branched-chain amino acids (BCAAs) associate with insulin resistance and type 2 diabetes. 3-Hydroxyisobutyrate (3-HIB) is a catabolic intermediate of the BCAA valine. Here we show that in a cohort of 4,942 men and women, circulating 3-HIB is elevated according to levels of hyperglycemia and established type 2 diabetes. In complementary cohorts with measures of insulin resistance, we found positive correlates for circulating 3-HIB concentrations with HOMA2-IR, as well as a transient increase in 3-HIB followed by a marked decrease after bariatric surgery and weight loss. During differentiation both white and brown adipocytes upregulate BCAA utilization and release increasing amounts of 3-HIB. Knockdown of the 3-HIB-forming enzyme HIBCH decreases release of 3-HIB and lipid accumulation in both cell types. Conversely, addition of 3-HIB to white and brown adipocyte cultures increases fatty acid uptake and modulated insulin-stimulated glucose uptake in a time-dependent manner. Finally, 3-HIB treatment decreases mitochondrial oxygen consumption and generation of reactive oxygen species (ROS) in white adipocytes, while increasing these measures in brown adipocytes. Our data establish 3-HIB as a novel adipocyte-derived regulator of adipocyte subtype-specific functions strongly linked to obesity, insulin resistance and type 2 diabetes.

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