Type 2 diabetes

This seminar examines genetic contributions to obesity and type 2 diabetes alongside their major health consequences. It challenges explanations based solely on personal behaviour and discusses how genetic studies can inform individualised care. The presentation also considers the discovery of treatment targets through research on disease-associated variants.

Dual-specificity phosphatase (Dusp8) has previously been identified as type 2 diabetes risk gene in humans that is highly expressed in the brain. Dusp8 acts as physiological inhibitor for mitogen-activated protein (MAP) kinases, which are involved in multiple CNS processes. Recently, we reported that hypothalamic Dusp8 acts as rheostat for Janus Kinase (Jnk) 1 in the arcuate nucleus and as critical gatekeeper for hypothalamus pituitary adrenals (HPA) axis functionality, hypothalamic insulin resistance and systemic glucose tolerance. In our follow-up studies, we aimed to dissect whether aberran

…MetS includes the development of type 2 diabetes, unprecedented weight gain, and dyslipidaemia. We hypothesised that SGAs disrupt mitochondrial function in the brain and periphery, and this may explain t

…Indeed, TALLYHO/JngJ mouse models of Type 2 diabetes are compulsive and anxious, with treatment with the Type 2 diabetes drug metformin generating partial rescue. Here, we aimed to establish the mechanisms behind this insulin-behavioural axis via proteomic analysis of brain and blood. Additionally, data from Genome-Wide Association studies (GWAS) of relevant disorders were compared using Ingenuity Pathway Analysis (IPA) (Qiagen). IPA analysis of proteomic results showed dysregul

The risk of developing Alzheimer’s disease (AD) is doubled in individuals with type 2 diabetes (T2D). While the prevalence of both diseases increases globally, the T2D-AD link remains to be elucidated. Ectopic accumulation of lipids (lipotoxicity) is a known consequence of T2D and has lately been suggested as a driver for AD. Angiogenesis and adult neurogenesis are thought to be affected in both diseases. Physical exercise acts preventively against AD and T2D and has been shown to stimulate angiogenesis and neurogenesis. In this study, we exposed animals from the db/db mouse model of T2D to ei

…are a hallmark of obesity and type 2 diabetes. Traditionally, the brain was thought to be insensitive to insulin, but our findings show that non-neuronal cells, specifically astrocytes located at the interface of neurons and blood vessels, sense and respond to insulin, thereby influencing systemic glucose control. Intrigued by these discoveries and recognising the potential of targeting these cells to

…and neuroimaging studies suggest that Type 2 Diabetes (T2DM) and Alzheimer's disease (AD) have a shared pathogenesis. Moreover, insulin resistance has been shown to impact hyperphosphorylation and aggregation of Tau making this an important risk factor for the detection of early

…is increased during ageing and in diabetes and plays a role in peripheral microvascular dysfunction. Whether MGO affects the brain microvasculature is unknown. The aim of this study is to investigate whether higher plasma MGO concentrations are cross-sectionally associated with markers for cerebral small vessel disease (CSVD) and with cognitive impairment. In participants of the Maastricht Study, a population-based cohort study oversampled with type 2 diabetes (age=59.

Sitagliptin, used for type-2 diabetes, inhibits dipeptidyl peptidase 4 (DPP-4), thus increasing insulin secretion. We found that sitagliptin protects the retina of diabetic animals, including type-1 diabetic animals, inhibiting nitrosative stress and neuroinflammation. We also showed that microglia-mediated neuroinflammation triggers retinal degeneration. Here, we investigated whether sitagliptin effects can be due to a direct inhibition of microglia reactivity, mediated by DPP-4 blockade, or if pleiotropic mechanisms can be involved. Primary mixed and organotypic rat retinal cell cultures and

Alzheimer’s disease (AD) and type 2 diabetes (T2D) share common features, including insulin resistance. Brain insulin resistance has been implicated as a key factor in the pathogenesis of AD. Recent studies have demonstrated that sodium–glucose cotransporter-2 inhibitor (SGLT2-i) and dipeptidyl peptidase-4 inhibitor (DPP4-i) improve insulin sensitivity and provide neuroprotection. However, the effects of these two inhibitors on the brain metabolism and insulin resistance remain uninvestigated.We developed a T2D–AD mouse model using a high-fat diet (HFD) for 19 weeks along with a single dose of

…in Alzheimer`s disease (AD) and type 2 diabetes (T2D). Importantly, analysis of the retina may provide a non-invasive approach with diagnostic and prognostic value for cognitive decline. In addition, T2D increases risk to suffer AD. Accordingly, we have analyzed structural and functional alterations, by spectral domain optical coherence tomography and electroretinography (ERG) respectively, in the retina from APP/PS1 (AD model), db/db (T2D model) and APP/PS1xdb/db (AD-T2D model) animals at 4 weeks of age, before the onset o

The increasing prevalence of obesity and type 2 diabetes (T2D) and associated morbidity and mortality emphasizes the need for a more complete understanding of the mechanisms mediating energy homeostasis to accelerate the identification of new medications. Recent reports indicate that obesity medication, 5-hydroxytryptamine (5-HT, serotonin)2C receptor (5-HT2CR) agonist lorcaserin improves glycemic control in association with weight loss in obese patients with T2D. We examined whether lorcaserin has a direct effect on insulin sensitivity and how this effect is achieved. We clarify that lorcaser