scholarly journals Measuring Insulin Resistance in Humans

2021 ◽  
pp. 1-12
Author(s):  
Vandhna R. Sharma ◽  
Samantha T. Matta ◽  
Morey W. Haymond ◽  
Stephanie T. Chung

<b><i>Background:</i></b> Insulin resistance is a pathophysiological condition associated with diabetes and cardiometabolic diseases that is characterized by a diminished tissue response to insulin action. Our understanding of this complex phenomenon and its role in the pathogenesis of cardiometabolic diseases is rooted in the discovery of insulin, its isolation and purification, and the challenges encountered with its therapeutic use. <b><i>Summary:</i></b> In this historical perspective, we explore the evolution of the term “insulin resistance” and demonstrate how advances in insulin and glucose analytics contributed to the recognition and validation of this metabolic entity. We identify primary discoveries which were pivotal in expanding our knowledge of insulin resistance, the challenges in measurement and interpretation, contemporary techniques, and areas of future exploration. <b><i>Key Message:</i></b> Measurements of insulin resistance are important tools for defining and treating cardiometabolic diseases. Accurate quantification of this pathophysiological entity requires careful consideration of the assumptions and pitfalls of the methodological techniques and the historical and clinical context when interpreting and applying the results.

1987 ◽  
Vol 22 (3) ◽  
pp. 286-291 ◽  
Author(s):  
Mitchell E Geffner ◽  
Solomon A Kaplan ◽  
Noelle Bersch ◽  
Barbara M Lippe ◽  
Wesley G Smith ◽  
...  

2017 ◽  
Vol 114 (40) ◽  
pp. E8478-E8487 ◽  
Author(s):  
Masahiro Konishi ◽  
Masaji Sakaguchi ◽  
Samuel M. Lockhart ◽  
Weikang Cai ◽  
Mengyao Ella Li ◽  
...  

Insulin receptors (IRs) on endothelial cells may have a role in the regulation of transport of circulating insulin to its target tissues; however, how this impacts on insulin action in vivo is unclear. Using mice with endothelial-specific inactivation of the IR gene (EndoIRKO), we find that in response to systemic insulin stimulation, loss of endothelial IRs caused delayed onset of insulin signaling in skeletal muscle, brown fat, hypothalamus, hippocampus, and prefrontal cortex but not in liver or olfactory bulb. At the level of the brain, the delay of insulin signaling was associated with decreased levels of hypothalamic proopiomelanocortin, leading to increased food intake and obesity accompanied with hyperinsulinemia and hyperleptinemia. The loss of endothelial IRs also resulted in a delay in the acute hypoglycemic effect of systemic insulin administration and impaired glucose tolerance. In high-fat diet-treated mice, knockout of the endothelial IRs accelerated development of systemic insulin resistance but not food intake and obesity. Thus, IRs on endothelial cells have an important role in transendothelial insulin delivery in vivo which differentially regulates the kinetics of insulin signaling and insulin action in peripheral target tissues and different brain regions. Loss of this function predisposes animals to systemic insulin resistance, overeating, and obesity.


1982 ◽  
Vol 243 (1) ◽  
pp. E15-E30 ◽  
Author(s):  
J. M. Olefsky ◽  
O. G. Kolterman ◽  
J. A. Scarlett

Resistance to the action of insulin can result from a variety of causes, including the formation of abnormal insulin or proinsulin molecules, the presence of circulating antagonists to insulin or the insulin receptor, or defects in insulin action at the target tissue level. Defects of the latter type are characteristic of obesity and of noninsulin-dependent diabetes mellitus. Analysis of the nature of the insulin resistance in those disorders has been investigated in intact subjects with the use of the euglycemic glucose clamp technique, and both insulin receptors and insulin-mediated glucose metabolism have been studied in adipocytes and monocytes from affected individuals. In both conditions, the cause of insulin resistance is heterogeneous. In some, insulin resistance appears to be due to a defect in the insulin receptor, whereas others have a defect both in the receptor and at the postreceptor level. In both groups, more severe insulin resistance is due to the postreceptor lesion and is correctable with appropriate therapy.


Babel ◽  
2011 ◽  
Vol 57 (1) ◽  
pp. 58-75
Author(s):  
Jorge L. Bueno-Alonso

The poetic insert known as <i>The Battle of Brunanburh</i> (<i>Anglo-Saxon Chronicle</i> 937) constitutes by no means one of the most interesting texts for the building of the Old English heroic geography. Its author, as Marsden states (2005: 86), “builds a sense of national destiny, using style, diction and imagery of heroic poetry”. There are many interesting issues to deal with when you want to revise how the elements Marsden quotes are used in the construction of a poem that uses history as a narrative device to build the inner story of the poem experimenting with the topics (style, diction, imagery) of heroic poetry. If the poem constitutes such a crucial text, if its emphasis is on “English nationalism” in an historical perspective rather than on individual heroics, as Marsden points out (2005: 86), it seems most evident that a careful consideration of these topics has to be made when translating the text into other languages. The aim of this article is to revisit the poem and its topics and to see how that careful consideration has been accomplished in several important English (Treharne 2004, Hamer 1970, Rodrigues 1996, Garmonsway 1953, Swanton 2000) and Spanish (Lerate & Lerate 2000, Bravo 1998, Bueno 2007) translations that consider the poem in isolation, in the context of the Anglo-Saxon Chronicle or as an excuse for poetic inspiration, i.e. the case of Borges’ 1964 and 1975 poems and Tennyson’s 1880 text.


2000 ◽  
Vol 88 (6) ◽  
pp. 2116-2122 ◽  
Author(s):  
Maria Niklasson ◽  
Peter Daneryd ◽  
Peter Lönnroth ◽  
Agneta Holmäng

Administration of testosterone (T) to oophorectomized (Ovx) female rats is followed by severe insulin resistance, localized to postreceptor cellular events in the muscle. In this study, intervention by exercise was introduced to examine whether circulatory adaptations are involved in insulin resistance. Two groups of Ovx rats were studied: one group was given T (Ovx+T); another group had free access to running wheels (Ovx+T+Ex). In addition, one control group (sham operated) was studied. Insulin sensitivity was measured with the euglycemic hyperinsulinemic clamp technique (submaximal) for 150 min. Muscle interstitial glucose and insulin concentrations were measured by microdialysis. The measurements showed that, in Ovx+T rats, the onset of insulin action was significantly ( P < 0.05) slower during the first 95 min of the clamp compared with that in Ovx+T+Ex and controls. Muscle interstitial concentrations of insulin but not glucose were lower in both Ovx+T and Ovx+T+Ex rats than in controls throughout the clamp. It was concluded that physical exercise prevented the slow onset of insulin action in Ovx+T rats without changing the distribution time of muscle interstitial insulin. The results indicate that hyperandrogenicity is characterized by delayed muscle insulin action. Physical exercise reverses these defects without any beneficial effect on muscle interstitial insulin concentrations.


2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A581-A582
Author(s):  
Ivan Augusto Rivera Nazario ◽  
Kyomara Hernandez Moya ◽  
Arnaldo Nieves Ortiz ◽  
Jose Ayala Rivera ◽  
Arnaldo Rojas Figueroa ◽  
...  

Abstract Acromegaly is an uncommon clinical syndrome that results from excessive secretion of growth hormone with an annual incidence of 6 to 8 cases per 1 million of individuals with a mean age of diagnosis between 40-45 years. Pituitary adenomas can be the principal reason for an overgrowth of the anterior pituitary somatotroph cells, and account for approximately one-third of all hormone-secreting pituitary adenomas with a prevalence of about 38-69 cases per 1 million and an incidence of 3-4 cases per 1 million individuals. The onset of acromegaly is insidious, and its progression is usually very slow. At the moment of diagnosis, approximately 75% of patients have presence of macro adenomas, but most cases are diagnosed after several laboratory workups and incidental brain imaging. A characteristic clinical presentation of pituitary adenomas could be secondary to mass effect. Metabolic presentation such as diabetes is one of the most common related conditions preceding the diagnosis of acromegaly. Clinical presentation with abrupt onset of DKA could be a determining factor on disease progression due to higher GH levels correlating with an increased prevalence of insulin resistance. We present a rare case of a 28y/o female G5P3A2 without previous PMHx who presented to ER with abdominal pain, general malaise, slurred speech, headache and gait difficulty of 3 days of evolution. Upon initial evaluation at ER patient was found with hyperglycemia of 317mg/dL, low central bicarbonate, high anion gap and positive serum ketones suggestive of DKA de novo. Based on neurological complaints, head CT performed showed an incidental parasellar/suprasellar/temporal hyperdense mass measuring 2.5cm x 2.6cm with optic chiasm compression features. Upon further specific questioning patient referred amenorrhea for the past 3 years, bitemporal hemianopsia, galactorrhea and marked facial feature changes, frontal bossing, weight gain, and acanthosis nigricans, for the past year. Pituitary adenoma workup revealed low prolactin levels (1.38), markedly increased growth hormone (501) and IGF-1 (893) suggesting diagnosis of acromegaly, most likely secondary to a functioning macroadenoma. Patient initially treated with Cabergoline, uncontrolled diabetes was managed and was referred to Neurosurgery service for further evaluation and tumor removal. Based on current literature, the incidence of acromegaly cases is low, more specifically when presenting with new onset diabetic ketoacidosis, insulin resistance and secondary to functioning macroadenomas. Medical awareness should be promoted to assess for careful consideration of signs and symptoms, workup, management and treatment to assess and minimize further health complications and physical burdens acromegaly and pituitary adenomas could pose for affected individuals.


2020 ◽  
Vol 244 (2) ◽  
pp. 353-367 ◽  
Author(s):  
Jiali Liu ◽  
Yue Li ◽  
Xiaoyan Zhou ◽  
Xi Zhang ◽  
Hao Meng ◽  
...  

High-fat diet (HFD) not only induces insulin resistance in liver, but also causes autophagic imbalance and metabolic disorders, increases chronic inflammatory response and induces mitochondrial dysfunction. Calcium/calmodulin-dependent protein kinase IV (CaMKIV) has recently emerged as an important regulator of glucose metabolism and skeletal muscle insulin action. Its activation has been involved in the improvement of hepatic and adipose insulin action. But the underlying mechanism is not fully understood. In the present study, we aimed to address the direct effects of CaMKIV in vivo and to evaluate the potential interaction of impaired insulin sensitivity and autophagic disorders in hepatic insulin resistance. Our results indicated obese mice receiving CaMKIV showed decreased blood glucose and serum insulin and improved insulin sensitivity as well as increased glucose tolerance compared with vehicle injection. Meanwhile, defective hepatic autophagy activity, impaired insulin signaling, increased inflammatory response and mitochondrial dysfunction in liver tissues which are induced by high-fat diet were also effectively alleviated by injection of CaMKIV. Consistent with these results, the addition of CaMKIV to the culture medium of BNL cl.2 hepatocytes markedly restored palmitate-induced hepatic insulin resistance and autophagic imbalance. These effects were nullified by blockade of cyclic AMP response element-binding protein (CREB), indicating the causative role of CREB in action of CaMKIV. Our findings suggested that CaMKIV restores hepatic autophagic imbalance and improves impaired insulin sensitivity via phosphorylated CREB signaling pathway, which may offer novel opportunities for treatment of obesity and diabetes.


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