A mathematical model reveals sex-specific changes in glucose and insulin tolerance during rat puberty and maturation

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Abstract

Aim

To evaluate the effects of maturation and sex on glucose metabolism during glucose tolerance (GTT) and insulin tolerance tests (ITT) in young and adult male and female rats by using two different approaches – the conventional, which uses area under the curve and glucose curve, and mathematical modeling that identifies parameters necessary for determining the function that models glucose metabolism.

Methods

Male and female rats at 3.5 and 12 months of age underwent standard GTT and ITT after overnight fasting. The parameters were identified by using Mathematica-module NonlinearModelFit [] for experimentally obtained data.

Results

When data were statistically analyzed, both sexes and age groups had similar glucose and insulin tolerance. In the mathematical model of GTT, parameters describing the rate of glucose concentration increase G’(0) and decrease G’ _I multiplied with maturation, with a concomitant decrease in the time point ( t _max, t _I ) of reaching maximum and minimum glucose concentration ( G _max, G ₀ ). The mathematical model of ITT for males was independent of age, unlike that for females, which had increased G’(0) and G’ _I, and more quickly recovered from hypoglycemia after maturation.

Conclusion

The mathematical model revealed female susceptibility to large glucose excursions, which are better reflected by ITT in young animals and by GTT in adults.

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Most cited references 35

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Pancreatic regulation of glucose homeostasis

Pia V. Röder, Bingbing Wu, Yixian Liu … (2016)

In order to ensure normal body function, the human body is dependent on a tight control of its blood glucose levels. This is accomplished by a highly sophisticated network of various hormones and neuropeptides released mainly from the brain, pancreas, liver, intestine as well as adipose and muscle tissue. Within this network, the pancreas represents a key player by secreting the blood sugar-lowering hormone insulin and its opponent glucagon. However, disturbances in the interplay of the hormones and peptides involved may lead to metabolic disorders such as type 2 diabetes mellitus (T2DM) whose prevalence, comorbidities and medical costs take on a dramatic scale. Therefore, it is of utmost importance to uncover and understand the mechanisms underlying the various interactions to improve existing anti-diabetic therapies and drugs on the one hand and to develop new therapeutic approaches on the other. This review summarizes the interplay of the pancreas with various other organs and tissues that maintain glucose homeostasis. Furthermore, anti-diabetic drugs and their impact on signaling pathways underlying the network will be discussed.

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Splanchnic lipolysis in human obesity.

Soren Nielsen, ZengKui Guo, C. Michael Johnson … (2004)

Elevated FFA concentrations have been shown to reproduce some of the metabolic abnormalities of obesity. It has been hypothesized that visceral adipose tissue lipolysis releases excess FFAs into the portal vein, exposing the liver to higher FFA concentrations. We used isotope dilution/hepatic vein catheterization techniques to examine whether intra-abdominal fat contributes a greater portion of hepatic FFA delivery in visceral obesity. Obese women (n = 24) and men (n = 20) with a range of obesity phenotypes, taken together with healthy, lean women (n = 12) and men (n = 12), were studied. Systemic, splanchnic, and leg FFA kinetics were measured. The results showed that plasma FFA concentrations were approximately 20% greater in obese men and obese women. The contribution of splanchnic lipolysis to hepatic FFA delivery ranged from less than 10% to almost 50% and increased as a function of visceral fat in women (r = 0.49, P = 0.002) and in men (r = 0.52, P = 0.002); the slope of the relationship was greater in women than in men (P < 0.05). Leg and splanchnic tissues contributed a greater portion of systemic FFA release in obese men and women than in lean men and women. We conclude that the contribution of visceral adipose tissue lipolysis to hepatic FFA delivery increases with increasing visceral fat in humans and that this effect is greater in women than in men.

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Glucotypes reveal new patterns of glucose dysregulation

Heather Hall, Dalia Perelman, Alessandra Breschi … (2018)

Diabetes is an increasing problem worldwide; almost 30 million people, nearly 10% of the population, in the United States are diagnosed with diabetes. Another 84 million are prediabetic, and without intervention, up to 70% of these individuals may progress to type 2 diabetes. Current methods for quantifying blood glucose dysregulation in diabetes and prediabetes are limited by reliance on single-time-point measurements or on average measures of overall glycemia and neglect glucose dynamics. We have used continuous glucose monitoring (CGM) to evaluate the frequency with which individuals demonstrate elevations in postprandial glucose, the types of patterns, and how patterns vary between individuals given an identical nutrient challenge. Measurement of insulin resistance and secretion highlights the fact that the physiology underlying dysglycemia is highly variable between individuals. We developed an analytical framework that can group individuals according to specific patterns of glycemic responses called “glucotypes” that reveal heterogeneity, or subphenotypes, within traditional diagnostic categories of glucose regulation. Importantly, we found that even individuals considered normoglycemic by standard measures exhibit high glucose variability using CGM, with glucose levels reaching prediabetic and diabetic ranges 15% and 2% of the time, respectively. We thus show that glucose dysregulation, as characterized by CGM, is more prevalent and heterogeneous than previously thought and can affect individuals considered normoglycemic by standard measures, and specific patterns of glycemic responses reflect variable underlying physiology. The interindividual variability in glycemic responses to standardized meals also highlights the personal nature of glucose regulation. Through extensive phenotyping, we developed a model for identifying potential mechanisms of personal glucose dysregulation and built a webtool for visualizing a user-uploaded CGM profile and classifying individualized glucose patterns into glucotypes.

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Author and article information

Journal

Journal ID (nlm-ta): Croat Med J

Journal ID (iso-abbrev): Croat. Med. J

Journal ID (publisher-id): CMJ

Title: Croatian Medical Journal

Publisher: Croatian Medical Schools

ISSN (Print): 0353-9504

ISSN (Electronic): 1332-8166

Publication date (Print): April 2020

Volume: 61

Issue: 2

Pages: 107-118

Affiliations

[1 ]Department of Medical Biology and Genetics, Faculty of Medicine Osijek, J. J. Strossmayer University of Osijek, Osijek, Croatia

[2 ]Department of Mathematics, J. J. Strossmayer University of Osijek, Osijek, Croatia

[3 ]Department of Biology, J. J. Strossmayer University of Osijek, Osijek, Croatia

[4 ]Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Szeged, Szeged, Hungary

[5 ]Cedars-Sinai Medical Center, International Research and Innovation in Medicine Program, Los Angeles, CA, United States

[6]The first two authors contributed equally.

Author notes

Correspondence to: Marija Heffer J. J. Strossmayer University of Osijek Faculty of Medicine Osijek Department of Medical Biology and Genetics Josipa Huttlera 4 HR-31000 Osijek, Croatia  mheffer@ 123456mefos.hr

Article

Publisher ID: CroatMedJ_61_0107

DOI: 10.3325/cmj.2020.61.107

PMC ID: 7230410

PubMed ID: 32378377

SO-VID: f61f2edf-2064-4ad5-adb9-dbad11062835

License:

This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

A mathematical model reveals sex-specific changes in glucose and insulin tolerance during rat puberty and maturation

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Abstract

Aim

Methods

Results

Conclusion

Related collections

HLA-G and immune tolerance in pregnancy

Most cited references 35

Pancreatic regulation of glucose homeostasis

Splanchnic lipolysis in human obesity.

Glucotypes reveal new patterns of glucose dysregulation

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