Insulin Resistance: Pathophysiology and Rationale for Treatment

Muntoni, Sergio; Muntoni, Sandro

doi:10.1159/000323395

Cited by 29 publications

(21 citation statements)

References 256 publications

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“…Compared to the data obtained in this study, the ability of dexamethasone to induce insulin resistance seems greater than the magnitude of insulin resistance observed in horses with PPID. It is well-established that cortisol excess causes insulin resistance in man, but the mechanisms responsible for this insulin resistance are poorly understood although possibly due to an impairment of peripheral insulin action located beyond the hormone-receptor binding step (Nosadini et al 1983) regarding the phosphatidylinositol 3-kinase (PI 3-K)-dependent pathway (Muntoni and Muntoni 2011).…”

Section: Discussionmentioning

confidence: 99%

Basal glucose metabolism and peripheral insulin sensitivity in equine pituitary pars intermedia dysfunction

Klinkhamer

Menheere

Kolk

2011

Veterinary Quarterly

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Background: Glucocorticoids are suggested to precipitate laminitis and induce insulin resistance in horses. Hypothesis/Objectives: To assess insulin sensitivity and the basal amount of glucose metabolized in equine pituitary pars intermedia dysfunction (PPID). Animals and methods: The euglycaemic hyperinsulinaemic clamp (EHC) technique was performed in seven horses with a diagnosis of PPID based on the presence of hypertrichosis and positive dexamethasone suppression-test results comprising one gelding and six mares with a mean age of 21.1 AE 5.8 (SD; range 15-34) years. Results were compared with those from five negative (healthy) controls comprising two geldings and two mares with a mean age of 10.0 AE 2.5 (range 7-13) years and six positive (diseased) controls comprising two geldings and four mares with a mean age of 12.5 AE 4.5 (range 8-21) years examined during the same period. Differences were assessed by means of the Mann-Whitney U test. Results: Mean basal rate of glucose metabolism (9.0 AE 4.2 versus 16.0 AE 5.2 mmol/kg BW/min; p ¼ 0.030) and mean glucose metabolism rate-to-plasma insulin concentration ratio (2.9 AE 1.6 versus 6.2 AE 2.7 Â 10 À6; p ¼ 0.048) were significantly lower in PPID horses than in negative controls, respectively. No differences were found between both control groups. Conclusions and clinical importance: In horses suffering from PPID it seems important to reduce the insulin resistance, thereby potentially decreasing the risk of laminitis as being a major complication of equine PPID. Plasma glucose concentration following fasting might be considered in the screening of horses for PPID.

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Section: Discussionmentioning

confidence: 99%

Basal glucose metabolism and peripheral insulin sensitivity in equine pituitary pars intermedia dysfunction

Klinkhamer

Menheere

Kolk

2011

Veterinary Quarterly

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“…Insulin therapy induces hypoglycemia, weight gain, and a range of adverse consequences of hyperinsulinemia with both short- and long-term outcomes (77–85). Newer antidiabetes classes may be used to delay insulin therapy in candidate patients with endogenous insulin production (19).…”

Section: β-Cell–centric Schema and Individualized Carementioning

confidence: 99%

The Time Is Right for a New Classification System for Diabetes: Rationale and Implications of the β-Cell–Centric Classification Schema

et al. 2016

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The current classification system presents challenges to the diagnosis and treatment of patients with diabetes mellitus (DM), in part due to its conflicting and confounding definitions of type 1 DM, type 2 DM, and latent autoimmune diabetes of adults (LADA). The current schema also lacks a foundation that readily incorporates advances in our understanding of the disease and its treatment. For appropriate and coherent therapy, we propose an alternate classification system. The β-cell–centric classification of DM is a new approach that obviates the inherent and unintended confusions of the current system. The β-cell–centric model presupposes that all DM originates from a final common denominator—the abnormal pancreatic β-cell. It recognizes that interactions between genetically predisposed β-cells with a number of factors, including insulin resistance (IR), susceptibility to environmental influences, and immune dysregulation/inflammation, lead to the range of hyperglycemic phenotypes within the spectrum of DM. Individually or in concert, and often self-perpetuating, these factors contribute to β-cell stress, dysfunction, or loss through at least 11 distinct pathways. Available, yet underutilized, treatments provide rational choices for personalized therapies that target the individual mediating pathways of hyperglycemia at work in any given patient, without the risk of drug-related hypoglycemia or weight gain or imposing further burden on the β-cells. This article issues an urgent call for the review of the current DM classification system toward the consensus on a new, more useful system.

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“…With increasing age of the child, there appears to be a gradual transition to a more important role of hGH in the regulation of IGF-I, along with increasing concentrations of growth hormone-binding proteins that are considered to reflect hGH receptor numbers [9,10]. Nutrition also markedly influences insulin secretion which has key regulatory roles for anabolic pathways as well as tissue and lipid deposition during early growth [11,12]. Glucose concentration is a key driver of insulin secretion, but the glucose-induced insulin secretion was shown to be markedly attenuated by a low protein supply [13].…”

mentioning

confidence: 99%

Early Influences of Nutrition on Postnatal Growth

Koletzko¹,

Beyer²,

Brands³

et al. 2013

Nestlé Nutrition Institute Workshop Series

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Health and nutrition modulate postnatal growth. The availability of amino acids and energy, and insulin and insulin-like growth factor-I (IGF-I) regulates early growth through the mTOR pathway. Amino acids and glucose also stimulate the secretion of IGF-I and insulin. Postnatal growth induces lasting, programming effects on later body size and adiposity in animals and in human observational studies. Rapid weight gain in infancy and the first 2 years was shown to predict increased obesity risk in childhood and adulthood. Breastfeeding leads to lesser high weight gain in infancy and reduces obesity risk in later life by about 20%, presumably partly due to the lower protein supply with human milk than conventional infant formula. In a large randomized clinical trial, we tested the hypothesis that reduced infant formula protein contents lower insulin-releasing amino acid concentrations and thereby decrease circulating insulin and IGF-I levels, resulting in lesser early weight gain and reduced later obesity risk (the 'Early Protein Hypothesis'). The results demonstrate that lowered protein in infant formula induces similar -but not equal -metabolic and endocrine responses and normalizes weight and BMI relative to breastfed controls at the age of 2 years. The results available should lead to enhanced efforts to actively promote, protect and support breastfeeding. For infants that are not breastfed or not fully breastfed, the use of infant formulas with lower protein contents but high protein quality appears preferable. Cows' milk as a drink provides high protein intake and should be avoided in infancy.

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Insulin Resistance: Pathophysiology and Rationale for Treatment

Cited by 29 publications

References 256 publications

Basal glucose metabolism and peripheral insulin sensitivity in equine pituitary pars intermedia dysfunction

Basal glucose metabolism and peripheral insulin sensitivity in equine pituitary pars intermedia dysfunction

The Time Is Right for a New Classification System for Diabetes: Rationale and Implications of the β-Cell–Centric Classification Schema

Early Influences of Nutrition on Postnatal Growth

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