Reduced expression of the
Indy (
I'm Not Dead, Yet) gene in
D. melanogaster and its homolog in
C. elegans prolongs life span and in
D. melanogaster augments mitochondrial biogenesis in a manner akin ...to caloric restriction. However, the cellular mechanism by which
Indy does this is unknown. Here, we report on the knockout mouse model of the mammalian
Indy (
mIndy) homolog,
SLC13A5. Deletion of
mIndy in mice (
mINDY
−/− mice) reduces hepatocellular ATP/ADP ratio, activates hepatic AMPK, induces PGC-1α, inhibits ACC-2, and reduces SREBP-1c levels. This signaling network promotes hepatic mitochondrial biogenesis, lipid oxidation, and energy expenditure and attenuates hepatic de novo lipogenesis. Together, these traits protect
mINDY
−/−
mice from the adiposity and insulin resistance that evolve with high-fat feeding and aging. Our studies demonstrate a profound effect of
mIndy on mammalian energy metabolism and suggest that mINDY might be a therapeutic target for the treatment of obesity and type 2 diabetes.
Display omitted
► A
mIndy (
SLC13A5) knockout mouse was generated ► Loss of
mIndy decreases hepatic ATP/ADP ratio and activates AMPK ►
mIndy deletion promotes mitochondrial biogenesis and energy expenditure ► Loss of
mIndy protects from diet- and age-associated insulin resistance
Context:
The circadian clock coordinates numerous metabolic processes with light-dark and feeding regimens. However, in humans it is unknown whether dietary patterns influence circadian rhythms.
...Objective:
We examined the effects of switching from a high-carbohydrate, low-fat diet to a low-carbohydrate, high fat (LC/HFD) isocaloric diet on the central and peripheral circadian clocks in humans.
Design:
Diurnal patterns of salivary cortisol and gene expression were analyzed in blood monocytes of 29 nonobese healthy subjects before and 1 and 6 weeks after the dietary switch. For this, we established a method of rhythm prediction by 3-time point data.
Results:
The centrally driven cortisol rhythm showed a phase delay 1 and 6 weeks after the dietary switch to a LC/HFD as well as an amplitude increase. The dietary switch altered diurnal oscillations of core clock genes (PER1, PER2, PER3, and TEF) and inflammatory genes (CD14, CD180, NFKBIA, and IL1B). The LC/HFD also affected the expression of nonoscillating genes contributing to energy metabolism (SIRT1) and fat metabolism (ACOX3 and IDH3A). Expression of clock genes but not of salivary cortisol in monocytes tightly correlated with levels of blood lipids and with expression of metabolic and inflammatory genes.
Conclusions:
Our results suggest that the modulation of the dietary fat and carbohydrate content alters the function of the central and peripheral circadian clocks in humans.
Aims
To investigate the best glucose monitoring strategy for maintaining euglycaemia by comparing self‐monitoring of blood glucose with continuous glucose monitoring, with or without an alarm ...function.
Methods
A 100‐day, randomized controlled study was conducted at four European centres, enrolling 160 patients with Type 1 or Type 2 diabetes, on multiple daily insulin injections or continuous subcutaneous insulin infusion. Participants were randomized to continuous glucose monitoring without alarms (n = 48), continuous glucose monitoring with alarms (n = 49) or self‐monitoring of blood glucose (n = 48).
Results
Time spent outside the glucose target during days 80–100 was 9.9 h/day for the continuous glucose monitoring without alarms group, 9.7 h/day for the continuous glucose monitoring with alarms group and 10.6 h/day for the self‐monitoring of blood glucose group (P = 0.18 and 0.08 compared with continuous glucose monitoring without and with alarms, respectively).The continuous glucose monitoring with alarms group spent less time in hypoglycaemia compared with the self‐monitoring of blood glucose group (1.0 h/day and 1.6 h/day, respectively; 95% CI −1.2 to −0.1; P = 0.030). Among those treated with continuous subcutaneous insulin infusion, time spent outside the glucose target was significantly different when comparing continuous glucose monitoring without alarms and self‐monitoring of blood glucose (−1.9 h/day; 95% CI −3.8 to 0.0; P = 0.0461) and when comparing continuous glucose monitoring with alarms and self‐monitoring of blood glucose (−2.4 h/day; 95% CI −4.1 to −0.5; P = 0.0134). There was no difference in HbA1c reduction from baseline in the three groups; however, the proportion of participants with a reduction of ≥ 6 mmol/mol (≥ 0.5%) was higher in the continuous glucose monitoring without alarms (27%) and continuous glucose monitoring with alarms groups (25%) than in the self‐monitoring of blood glucose group (10.6%).
Conclusions
This study shows that the use of continuous glucose monitoring reduces time spent outside glucose targets compared with self‐monitoring of blood glucose, especially among users of insulin pumps.
What's new?
In this study, time spent outside glucose target was not significantly different between continuous glucose monitoring with and without alarm groups. The proportion of participants with an HbA1c concentration reduction ≥ 6 mmol/mol (≥ 0.5%) was similar in the two continuous glucose monitoring groups.
This indicates that, for certain individuals, continuous glucose monitoring without alarms may be as beneficial and safe as continuous glucose monitoring with alarms compared with conventional self‐monitoring of blood glucose.
High frequency of alarms, especially false alarms, may lead to alarm fatigue, making users less likely to respond appropriately.
Insulin clearance is decreased in type 2 diabetes mellitus (T2DM) for unknown reasons. Subjects with metabolic syndrome are hyperinsulinemic and have an increased risk of T2DM. We aimed to ...investigate the relationship between hepatic insulin clearance (HIC) and different components of metabolic syndrome and tested the hypothesis that HIC may predict the risk of metabolic syndrome.
Individuals without diabetes from the Metabolic Syndrome Berlin Brandenburg (MeSyBePo) study (800 subjects with the baseline examination and 189 subjects from the MeSyBePo recall study) underwent an oral glucose tolerance test (OGTT) with assessment of insulin secretion (insulin secretion rate ISR) and insulin sensitivity. Two indices of HIC were calculated.
Both HIC indices showed lower values in subjects with metabolic syndrome (P < 0.001) at baseline. HIC indices correlate inversely with waist circumference, diastolic blood pressure, fasting glucose, triglycerides, and OGTT-derived insulin secretion index. During a mean follow-up of 5.1 ± 0.9 years, 47 individuals developed metabolic syndrome and 33 subjects progressed to impaired glucose metabolism. Both indices of HIC showed a trend of an association with increased risk of metabolic syndrome (HICC-peptide odds ratio 1.13 95% CI 0.97-1.31, P = 0.12, and HICISR 1.38 0.88-2.17, P = 0.16) and impaired glucose metabolism (HICC-peptide 1.12 0.92-1.36, P = 0.26, and HICISR 1.31 0.74-2.33 P = 0.36), although point estimates reached no statistical significance.
HIC was associated with different components of metabolic syndrome and markers of insulin secretion and insulin sensitivity. Decreased HIC may represent a novel pathophysiological mechanism of the metabolic syndrome, which may be used additionally for early identification of high-risk subjects.
Background
Diabetes mellitus (DM) is a risk factor for periodontitis. Data on risk-modifying factors for periodontitis in diabetes patients are limited.
Aims
We tested whether sex, age, type of ...diabetes, metabolic state, comorbidities, complications, measures of well-being and quality of life are predicting periodontitis in a German diabetes outpatient cohort.
Methods
In total, 1180 out of 1293 participating DM patients completed questionnaires on quality of life, dental hygiene and health. All patients also filled out a modified version of the periodontitis risk questionnaire by the American Association for Periodontology, from which the status of “assumed periodontitis” was deducted. In a subset of participants (
n
= 461), we measured or inquired the most recent Community Parodontal Index (CPI), providing an objective measure for clinically diagnosed periodontitis. For all subjects, DM history and phenotype, major metabolic parameters (HbA1c, BMI, LDL and total cholesterol levels), general health risk factors, comorbidities and medication were collected.
Results
Clinically diagnosed (CPI > 2) and assumed periodontitis was detected in 60–67% of our patients. Male sex and oral health-related quality of life were associated with clinically diagnosed periodontitis. Male sex, age, smoking, dental hygiene, dental control and diabetes-related quality of life independently predicted assumed periodontitis.
Conclusion
In DM patients, quality of life and lifestyle factors which systemically alter microvascular and immunological functions seem to predict periodontitis. Further studies are needed for replication and for pathomechanistic clarification.
Topographic and isostatic mass anomalies affect the external gravity field of the Earth. Therefore, these effects also exist in the gravity gradients observed, e.g., by the satellite gravity ...gradiometry mission GOCE (
G
ravity and Steady-State
O
cean
C
irculation
E
xperiment). The downward continuation of the gravitational signals is rather difficult because of the high-frequency behaviour of the combined topographic and isostatic effects. Thus, it is preferable to smooth the gravity field by some topographic-isostatic reduction. In this paper the focus is on the modelling of masses in the space domain, which can be subdivided into different mass elements and evaluated with analytical, semi-analytical and numerical methods. Five alternative mass elements are reviewed and discussed: the tesseroid, the point mass, the prism, the mass layer and the mass line. The formulae for the potential, the attraction components and the Marussi tensor of second-order potential derivatives are provided. The formulae for different mass elements and computation methods are checked by assuming a synthetic topography of constant height over a spherical cap and the position of the computation point on the polar axis. For this special situation an exact analytical solution for the tesseroid exists and a comparison between the analytical solution of a spherical cap and the modelling of different mass elements is possible. A comparison of the computation times shows that modelling by tesseroids with different methods produces the most accurate results in an acceptable computation time. As a numerical example, the Marussi tensor of the topographic effect is computed globally using tesseroids calculated by Gauss–Legendre cubature (3D) on the basis of a digital height model. The order of magnitude in the radial-radial component is about ± 8 E.U.
Aims/hypothesis
Glucagon reduces body weight by modifying food intake, glucose/lipid metabolism and energy expenditure. All these physiological processes are also controlled by fibroblast growth ...factor 21 (FGF-21), a circulating hepatokine that improves the metabolic profile in obesity and type 2 diabetes. Animal experiments have suggested a possible interaction between glucagon and FGF-21 however, the metabolic consequences of this crosstalk are not understood.
Methods
The effects of exogenous glucagon on plasma FGF-21 levels and lipolysis were evaluated in healthy volunteers and humans with type 1 diabetes, as well as in rodents with streptozotocin (STZ)-induced insulinopenic diabetes. In vitro, the role of glucagon on FGF-21 secretion and lipolysis was studied using isolated primary rat hepatocytes and adipocytes.
Fgf-21
expression in differentiated rat pre-adipocytes was suppressed by small interfering RNA and released FGF-21 was immunoneutralised by polyclonal antibodies.
Results
Glucagon induced lipolysis in healthy human volunteers, patients with type 1 diabetes, mice and rats with STZ-induced insulinopenic diabetes, and in adipocytes isolated from diabetic and non-diabetic animals. In addition, glucagon increased circulating FGF-21 in healthy humans and rodents, as well as in patients with type 1 diabetes, and insulinopenic rodents. Glucagon stimulated FGF-21 secretion from isolated primary hepatocytes and adipocytes derived from animals with insulinopenic diabetes. Furthermore, FGF-21 stimulated lipolysis in primary adipocytes isolated from non-diabetic and diabetic rats. Reduction of
Fgf-21
expression (by approximately 66%) or immunoneutralisation of released FGF-21 markedly attenuated glucagon-stimulated lipolysis in adipocytes.
Conclusions/interpretation
These results indicate that glucagon increases circulating FGF-21 independently of endogenous insulin levels. FGF-21 participates in glucagon-induced stimulation of lipolysis.
There is growing recognition that gastrointestinal dysfunction is common in Parkinson's disease (PD). Virtually all parts of the gastrointestinal tract can be affected, in some cases early in the ...disease course. Weight loss is common but poorly understood in people with PD. Dysphagia can result from dysfunction at the mouth, pharynx, and oesophagus and may predispose individuals to aspiration (accidental inhalation of food or liquid). Gastroparesis can produce various symptoms in patients with PD and may cause erratic absorption of drugs given to treat the disorder. Bowel dysfunction can consist of both slowed colonic transit with consequent reduced bowel-movement frequency, and difficulty with the act of defecation itself with excessive straining and incomplete emptying. Recognition of these gastrointestinal complications can lead to earlier and potentially more effective therapeutic intervention.
Currently, the economy of Middle Eastern countries relies heavily on fossil fuel sources. The direct and indirect adverse consequences of fossil fuel utilization for power generation enforce the ...region’s countries to raise the share of renewable energy. In this context, various incentive policies have been developed to encourage the residential and industrial sectors to support a portion of energy needs through renewable energy resources. In this case, a solar water heating system (SWHS) as an application of solar thermal technology provides some of the heat energy requirements for domestic hot water (DHW) and space heating, supported conventionally by electricity or natural gas, or even other fossil fuels. This paper reviews the feasibility of the SWHS in the Middle East region from technical and economical standpoints and investigates some of the progress, challenges, and barriers toward this market. The pay-back times and CO2 emission reduction under different incentive frameworks and configurations of each system have been assessed in this context. Furthermore, the advantages and weaknesses of the SWHS in several countries have been reported. Finally, various guidelines have been proposed to enhance the development of this technology.
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