Deterioration of Insulin Sensitivity and Glucose Effectiveness With Age and Hypertension

Burattini, Roberto; Nardo, Francesco Di; Boemi, Massimo; Fumelli, P.

doi:10.1016/j.amjhyper.2005.07.001

Cited by 26 publications

(27 citation statements)

References 27 publications

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“…It is noteworthy that in the 24-month old rats not only were tissue OGlcNAc levels increased, but the animals were also markedly insulin resistant as evident by the ~4-fold increase in serum insulin levels. This is consistent with reports of impaired glucose tolerance and decreased insulin sensitivity associated with aging (Basu et al, 2003;Burattini et al, 2006), which could exacerbate the imbalance between death and survival signals and contribute to increased apoptosis and cell loss associated with aging and senescence (Zhang and Herman, 2002). It is important to note that, while tempting to suggest that the increase in skeletal muscle O-GlcNAc is causative in the development of insulin resistance seen with aging, such a relationship cannot be established from these data.…”

Section: Discussionsupporting

confidence: 49%

Aging leads to increased levels of protein O-linked N-acetylglucosamine in heart, aorta, brain and skeletal muscle in Brown-Norway rats

et al. 2008

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Changes in the levels of O-linked N-acetylglucosamine (O-GlcNAc) on nucleocytoplasmic protein have been associated with a number of age-related diseases such as Alzheimer's and diabetes; however, there is relatively little information regarding the impact of age on tissue O-GlcNAc levels. Therefore, the goal of this study was to determine whether senescence was associated with alterations in O-GlcNAc in heart, aorta, brain and skeletal muscle and if so whether there were also changes in the expression of enzymes critical in regulating O-GlcNAc levels, namely, O-GlcNAc transferase (OGT), O-GlcNAcase and glutamine:fructose-6-phosphate amidotransferase (GFAT). Tissues were harvested from 5-and 24-month old Brown-Norway rats; UDP-GlcNAc, a precursor of O-GlcNAc was assessed by HPLC, O-GlcNAc and OGT levels were assessed by immunoblot analysis and GFAT1/2, OGT, O-GlcNAcase mRNA levels were determined by RT-PCR. In the 24-month old animals serum insulin and triglyceride levels were significantly increased compared to the 5-month old group; however, glucose levels were unchanged. Protein O-GlcNAc levels were significantly increased with age (30-107 %) in all tissues examined; however, paradoxically the expression of OGT, which catalyzes O-GlcNAc formation, was decreased by ~30% in the heart, aorta and brain. In the heart increased O-GlcNAc was associated with increased UDP-GlcNAc levels and elevated GFAT mRNA while in other tissues we found no difference in UDP-GlcNAc or GFAT mRNA levels. These results demonstrate that senescence is associated with increased O-GlcNAc levels in multiple tissues and support the notion that dysregulation of pathways leading to O-GlcNAc formation may play an important role in the development of age-related diseases.

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Section: Discussionsupporting

confidence: 49%

Aging leads to increased levels of protein O-linked N-acetylglucosamine in heart, aorta, brain and skeletal muscle in Brown-Norway rats

et al. 2008

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“…Under our clinical settings, a significant 56% reduction of S I was observed in our normoglycemic, insulin-resistant hypertensive patients, compared to our control N-group (Table 2). This finding is consistent with the well recognized association between insulin resistance and hypertension assessed from traditional, GKMM-based and clamp-based insulin sensitivity indexes [9,10,18,22,23,26,33]. On the other hand, no significant change of glucose effectiveness, S G , between our age-matched H and N groups meets our previous finding that non-insulin-mediated glucose uptake depends on age and is irrespective of insulin resistance [9].…”

Section: Discussionsupporting

confidence: 94%

“…Significant deterioration of insulin sensitivity in hypertension has been reported after quantification of insulin-sensitivity indexes by the euglycemic-hyperinsulinemic clamp technique [13,18,23], and by applying the glucose kinetics minimal model (GKMM) to interpret insulinemia and glycemia data obtained from either frequently sampled intravenous glucose tolerance test (FSIGTT) [9,22,26,33] or frequently sampled oral glucose tolerance test (FSOGTT) [10]. Among these methods, the GKMM-based interpretation of FSIGTT data has the advantage to provide simultaneous estimates of two other parameters, beyond S I , which are useful to complement the assessment of glucose tolerance.…”

Section: Introductionmentioning

confidence: 99%

Dynamics of insulin action in hypertension: assessment from minimal model interpretation of intravenous glucose tolerance test data

Burattini

Morettini

Nardo

et al. 2011

Med Biol Eng Comput

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Based on glucose kinetics minimal model (GKMM) interpretation of frequently sampled intravenous glucose tolerance test (FSIGTT), the aim was to broaden the characterization of insulin-mediated glucose disposal in hypertension by aid of a dynamic insulin sensitivity index, S(D)(I), and the related efficiency, η = S(D)(I) / S(I), of the metabolic system to convert the maximal individual response capacity, measured by S (I), into an effective insulin control on glucose. The C-peptide minimal model (CPMM) was used to interpret the role of β-cell function. Plasma glucose, insulin, and C-peptide concentrations were measured, during a 5-h FSIGTT, in eighteen normoglycemic individuals: ten hypertensive patients (H-group) and eight normotensive subjects (N-group) with no metabolic syndrome. Compared to our N-group, the H-group showed a significant (P < 0.05) reduction of both S(I) (56%) and S(D)(I) (50%), no significant change of η, a significant increase of both the first-phase β-cell responsiveness to glucose (105%) and total insulin secretion (55%), and no significant change in disposition indexes, defined as the product of insulin sensitivity (either S(I) and S(D)(I)) and β-cell responsiveness. These findings suggest that, in spite of no change of efficiency, insulin resistance in normoglycemic hypertensive patients is primarily compensated by an increase in first-phase insulin secretion to preserve glucose tolerance to intravenous glucose load.

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“…An association among insulin resistance (decreased sensitivity or responsiveness to the metabolic actions of insulin), hyperinsulinemia, and hypertension is generally recognized [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16]. Demonstration that essential hypertension is an insulin-resistant state in its own right implied its involvement in the insulin resistance syndrome, later transmuted into the metabolic syndrome (MS) [1,2,17,18].…”

Section: Introductionmentioning

confidence: 99%

Insulin action and secretion in hypertension in the absence of metabolic syndrome: model-based assessment from oral glucose tolerance test

et al. 2009

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Deterioration of Insulin Sensitivity and Glucose Effectiveness With Age and Hypertension

Cited by 26 publications

References 27 publications

Aging leads to increased levels of protein O-linked N-acetylglucosamine in heart, aorta, brain and skeletal muscle in Brown-Norway rats

Aging leads to increased levels of protein O-linked N-acetylglucosamine in heart, aorta, brain and skeletal muscle in Brown-Norway rats

Dynamics of insulin action in hypertension: assessment from minimal model interpretation of intravenous glucose tolerance test data

Insulin action and secretion in hypertension in the absence of metabolic syndrome: model-based assessment from oral glucose tolerance test

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