Physiology of glucose homeostasis

Gerich, John E.

doi:10.1046/j.1463-1326.2000.00085.x

Cited by 148 publications

(114 citation statements)

References 43 publications

(51 reference statements)

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“…Conceivably, the improved glucose homeostasis with DPD could result from a correction in dysregulated endogenous glucose production and/or systemic glucose clearance (37). Indeed, select AAs are key gluconeogenic substrates in the liver (38), and in the present study DPD blunted endogenous glucose production as assessed by pyruvate tolerance testing.…”

Section: Discussionsupporting

confidence: 47%

A liver stress-endocrine nexus promotes metabolic integrity during dietary protein dilution

Maida

Zota

Sjøberg

et al. 2016

Journal of Clinical Investigation

144

260

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Section: Discussionsupporting

confidence: 47%

A liver stress-endocrine nexus promotes metabolic integrity during dietary protein dilution

Maida

Zota

Sjøberg

et al. 2016

Journal of Clinical Investigation

144

260

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“…The glucose uptake of the brain and the red blood cells is not affected by insulin and is thus easily separated from the dynamic profile. The remaining glucose uptake profile was subdivided with the proportions 20 % to adipose tissue and 80 % to muscle tissue glucose uptake [197]. We ignored the liver glucose uptake since most meal glucose is directly absorbed by the liver before entering the plasma and is thus not accounted for by the Dalla Man model.…”

Section: Creating a Mathematical Link Using Dynamic Constraintsmentioning

confidence: 99%

Insulin signaling dynamics in human adipocytes : Mathematical modeling reveals mechanisms of insulin resistance in type 2 diabetes

Nyman¹

2014

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Type 2 diabetes is characterized by raised blood glucose levels caused by an insufficient insulin control of glucose homeostasis. This lack of control is expressed both through insufficient release of insulin by the pancreatic beta-cells, and through insulin resistance in the insulin-responding tissues. We find insulin resistance of the adipose tissue particularly interesting since it appears to influence other insulin-responding tissues, such as muscle and liver, to also become insulin resistant.The insulin signaling network is highly complex with cross-interacting intermediaries, positive and negative feedbacks, etc. To facilitate the mechanistic understanding of this network, we obtain dynamic, information-rich data and use model-based analysis as a tool to formally test different hypotheses that arise from the experimental observations. With dynamic mathematical models, we are able to combine knowledge and experimental data into mechanistic hypotheses, and draw conclusions such as rejection of hypotheses and prediction of outcomes of new experiments.We aim for an increased understanding of adipocyte insulin signaling and the underlying mechanisms of the insulin resistance that we observe in adipocytes from subjects diagnosed with type 2 diabetes. We also aim for a complete picture of the insulin signaling network in primary human adipocytes from normal and diabetic subjects with a link to relevant clinical parameters: plasma glucose and insulin. Such a complete picture of insulin signaling has not been presented before. Not for adipocytes and not for other types of cells.In this thesis, I present the development of the first comprehensive insulin signaling model that can simulate both normal and diabetic data from adipocytes -and that is linked to a whole-body glucose-insulin model. In the linking process we conclude that at least two glucose uptake parameters differ between the in vivo and in vitro conditions (Paper I). We also perform a model analysis of the early insulin signaling dynamics in rat adipocytes and conclude that internalization is important for an apparent reversed order of phosphorylation seen in these cells (Paper II). In the development of the first version of the comprehensive insulin signaling model, we introduce a key parameter for the diabetic state -an attenuated feedback (Paper III). We finally continue to build on the comprehensive model and include signaling to nuclear transcription via ERK and report substantial crosstalk in the insulin signaling network (Paper IV). Populärvetenskaplig sammanfattningTyp 2-diabetes är en vanligt förekommande sjukdom där kroppens vävnader förlorar sin känslighet mot hormonet insulin. Insulinets uppgift är att hålla en jämn blodsockernivå dygnet runt. Insulin utsöndras i samband med måltider och påverkar muskel-och fettvävnader att ta upp socker och levern att sluta producera socker. Det är viktigt att hålla en jämn blodsockernivå eftersom låga nivåer kan vara direkt dödligt och höga nivåer är skadligt för blodkärlen, vilket i sin tur kan led...

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“…The vital role of kidney in human physiology by helping maintain glucose balance was later described in 1938 by Bergman and colleagues [3]. More recent data confirm that normoglycaemia is accomplished through the balanced actions of glucose absorption in the gastrointestinal tract, glycogenolysis in the liver, glucose reabsorption and glucose excretion in the kidney along with gluconeogenesis in the liver and the kidney [4,5]. Under normal conditions,~180 g of glucose are filtered by the kidney glomerulus per day, and virtually the entire amount is reabsorbed in the proximal tubule [6].…”

mentioning

confidence: 90%

“…Meanwhile,~10% is reabsorbed in the S3 regimen, where SGLT1 and GLUT1 are located [7]. Glycosuria will appear if the filtered glucose exceeds the glucose threshold of 180 mg/dl or the filtered glucose load exceeds 375 mg/min or if the renal reabsorptive capacity is reduced [4,5]. More recently, glycosuria can be induced by the SGLT2 inhibitors.…”

mentioning

confidence: 99%

Luseogliflozin and other sodium-glucose cotransporter 2 inhibitors: no enemy but time?

Pafili

Παπάνας

2015

Expert Opinion on Pharmacotherapy

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Physiology of glucose homeostasis

Cited by 148 publications

References 43 publications

A liver stress-endocrine nexus promotes metabolic integrity during dietary protein dilution

A liver stress-endocrine nexus promotes metabolic integrity during dietary protein dilution

Insulin signaling dynamics in human adipocytes : Mathematical modeling reveals mechanisms of insulin resistance in type 2 diabetes

Luseogliflozin and other sodium-glucose cotransporter 2 inhibitors: no enemy but time?

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