Stephanie Kullmann

Bio: Stephanie Kullmann is an academic researcher from University of Tübingen. The author has contributed to research in topics: Insulin & Insulin resistance. The author has an hindex of 32, co-authored 64 publications receiving 2876 citations.

Brain Insulin Resistance at the Crossroads of Metabolic and Cognitive Disorders in Humans

Abstract: Ever since the brain was identified as an insulin-sensitive organ, evidence has rapidly accumulated that insulin action in the brain produces multiple behavioral and metabolic effects, influencing eating behavior, peripheral metabolism, and cognition. Disturbances in brain insulin action can be observed in obesity and type 2 diabetes (T2D), as well as in aging and dementia. Decreases in insulin sensitivity of central nervous pathways, i.e., brain insulin resistance, may therefore constitute a joint pathological feature of metabolic and cognitive dysfunctions. Modern neuroimaging methods have provided new means of probing brain insulin action, revealing the influence of insulin on both global and regional brain function. In this review, we highlight recent findings on brain insulin action in humans and its impact on metabolism and cognition. Furthermore, we elaborate on the most prominent factors associated with brain insulin resistance, i.e., obesity, T2D, genes, maternal metabolism, normal aging, inflammation, and dementia, and on their roles regarding causes and consequences of brain insulin resistance. We also describe the beneficial effects of enhanced brain insulin signaling on human eating behavior and cognition and discuss potential applications in the treatment of metabolic and cognitive disorders.

The obese brain: Association of body mass index and insulin sensitivity with resting state network functional connectivity

Abstract: Obesity is a key risk factor for the development of insulin resistance, Type 2 diabetes and associated diseases; thus, it has become a major public health concern. In this context, a detailed understanding of brain networks regulating food intake, including hormonal modulation, is crucial. At present, little is known about potential alterations of cerebral networks regulating ingestive behavior. We used "resting state" functional magnetic resonance imaging to investigate the functional connectivity integrity of resting state networks (RSNs) related to food intake in lean and obese subjects using independent component analysis. Our results showed altered functional connectivity strength in obese compared to lean subjects in the default mode network (DMN) and temporal lobe network. In the DMN, obese subjects showed in the precuneus bilaterally increased and in the right anterior cingulate decreased functional connectivity strength. Furthermore, in the temporal lobe network, obese subjects showed decreased functional connectivity strength in the left insular cortex. The functional connectivity magnitude significantly correlated with body mass index (BMI). Two further RSNs, including brain regions associated with food and reward processing, did not show BMI, but insulin associated functional connectivity strength. Here, the left orbitofrontal cortex and right putamen functional connectivity strength was positively correlated with fasting insulin levels and negatively correlated with insulin sensitivity index. Taken together, these results complement and expand previous functional neuroimaging findings by demonstrating that obesity and insulin levels influence brain function during rest in networks supporting reward and food regulation.

Impaired insulin action in the human brain: causes and metabolic consequences

Abstract: Over the past few years, evidence has accumulated that the human brain is an insulin-sensitive organ. Insulin regulates activity in a limited number of specific brain areas that are important for memory, reward, eating behaviour and the regulation of whole-body metabolism. Accordingly, insulin in the brain modulates cognition, food intake and body weight as well as whole-body glucose, energy and lipid metabolism. However, brain imaging studies have revealed that not everybody responds equally to insulin and that a substantial number of people are brain insulin resistant. In this Review, we provide an overview of the effects of insulin in the brain in humans and the relevance of the effects for physiology. We present emerging evidence for insulin resistance of the human brain. Factors associated with brain insulin resistance such as obesity and increasing age, as well as possible pathogenic factors such as visceral fat, saturated fatty acids, alterations at the blood-brain barrier and certain genetic polymorphisms, are reviewed. In particular, the metabolic consequences of brain insulin resistance are discussed and possible future approaches to overcome brain insulin resistance and thereby prevent or treat obesity and type 2 diabetes mellitus are outlined.

Food related processes in the insular cortex

Abstract: The insular cortex is a multimodal brain region with regional cytoarchitectonic differences indicating various functional specializations. As a multisensory neural node, the insular cortex integrates perception, emotion, interoceptive awareness, cognition, and gustation. Regarding the latter, predominantly the anterior part of the insular cortex is regarded as the primary taste cortex. In this review, we will specifically focus on the involvement of the insula in food processing and on multimodal integration of food-related items. Influencing factors of insular activation elicited by various foods range from calorie-content to the internal physiologic state, body mass index or eating behavior. Sensory perception of food-related stimuli including seeing, smelling, and tasting elicits increased activation in the anterior and mid-dorsal part of the insular cortex. Apart from the pure sensory gustatory processing, there is also a strong association with the rewarding/hedonic aspects of food items, which is reflected in higher insular activity and stronger connections to other reward-related areas. Interestingly, the processing of food items has been found to elicit different insular activation in lean compared to obese subjects and in patients suffering from an eating disorder (anorexia nervosa, bulimia nervosa). The knowledge of functional differences in the insular cortex opens up the opportunity for possible noninvasive treatment approaches for obesity and eating disorders. To target brain functions directly, real-time functional magnetic resonance imaging neurofeedback offers a state-of-the-art tool to learn to control the anterior insular cortex activity voluntarily. First evidence indicates that obese adults have an enhanced ability to regulate the anterior insular cortex.

Classification and diagnosis of diabetes

Abstract: 1. Type 1 diabetes (due to b-cell destruction, usually leading to absolute insulin deficiency) 2. Type 2 diabetes (due to a progressive insulin secretory defect on the background of insulin resistance) 3. Gestational diabetes mellitus (GDM) (diabetes diagnosed in the second or third trimester of pregnancy that is not clearly overt diabetes) 4. Specific types of diabetes due to other causes, e.g., monogenic diabetes syndromes (such as neonatal diabetes and maturity-onset diabetes of the young [MODY]), diseases of the exocrine pancreas (such as cystic fibrosis), and drugor chemical-induced diabetes (such as in the treatment of HIV/AIDS or after organ transplantation)

Beta-band oscillations--signalling the status quo?

Abstract: In this review, we consider the potential functional role of beta-band oscillations, which at present is not yet well understood. We discuss evidence from recent studies on top-down mechanisms involved in cognitive processing, on the motor system and on the pathophysiology of movement disorders that suggest a unifying hypothesis: beta-band activity seems related to the maintenance of the current sensorimotor or cognitive state. We hypothesize that beta oscillations and/or coupling in the beta-band are expressed more strongly if the maintenance of the status quo is intended or predicted, than if a change is expected. Moreover, we suggest that pathological enhancement of beta-band activity is likely to result in an abnormal persistence of the status quo and a deterioration of flexible behavioural and cognitive control.

Mechanisms of Insulin Action and Insulin Resistance

Abstract: The 1921 discovery of insulin was a Big Bang from which a vast and expanding universe of research into insulin action and resistance has issued. In the intervening century, some discoveries have ma...

Behavioral interpretations of intrinsic connectivity networks

Abstract: An increasingly large number of neuroimaging studies have investigated functionally connected networks during rest, providing insight into human brain architecture. Assessment of the functional qualities of resting state networks has been limited by the task-independent state, which results in an inability to relate these networks to specific mental functions. However, it was recently demonstrated that similar brain networks can be extracted from resting state data and data extracted from thousands of task-based neuroimaging experiments archived in the BrainMap database. Here, we present a full functional explication of these intrinsic connectivity networks at a standard low order decomposition using a neuroinformatics approach based on the BrainMap behavioral taxonomy as well as a stratified, data-driven ordering of cognitive processes. Our results serve as a resource for functional interpretations of brain networks in resting state studies and future investigations into mental operations and the tasks that drive them.