We suggest to sub-classify L-cells based on their differential peptide contents as well as their differential expression of nutrient sensors, which ultimately determine the secretory responses to different stimuli. A second purpose of this review is to describe and discuss the most frequently used experimental models for functional L-cell studies, highlighting their benefits and limitations. We conclude that no experimental model is perfect and that a comprehensive understanding must be built on results from a combination of models.Primary cilia (PC) are microtubule-based organelles that are present on nearly all thyroid follicle cells and play an important role in physiological development and in maintaining the dynamic homeostasis of thyroid follicles. PC are generally lost in many thyroid cancers (TCs), and this loss has been linked to the malignant transformation of thyrocytes, which is regulated by PC-mediated signaling reciprocity between the stroma and cancer cells. Restoring PC on TC cells is a possible promising therapeutic strategy, and the therapeutic response and prognosis of TC are associated with the presence or absence of PC. This review mainly discusses the role of PC in the normal thyroid and TC as well as their potential clinical utility.
  Familial partial lipodystrophy type 3 (FPLD3) is a very rare autosomal dominant genetic disorder which is caused by mutations in the peroxisome proliferator activated receptor gamma (
  ) gene. It is characterized by a partial loss of adipose tissue leading to subnormal leptin secretion and metabolic complications. Metreleptin, a synthetic analogue of human leptin, is an effective treatment for generalized lipodystrophies, but the evidence for efficacy in patients with FPLD3 is scarce.
 
  We present a 61-year-old woman, initially misdiagnosed as type 1 diabetes since the age of 29, with severe insulin resistance, who gradually displayed a more generalized form of lipoatrophy and extreme hypertriglyceridemia, hypertension and multiple manifestations of cardiovascular disease. She was found to carry a novel mutation leading to PPARG
  variant. After six months of metreleptin treatment, HbA1c decreased from 10 to 7.9% and fasting plasma triglycerides were dramatically reduced from 2.919 mg/dl to 198 mg/dl.
 
  This case highlights the importance of early recognition of FPLD syndromes otherwise frequently observed as difficult-to-classify and manages diabetes cases, in order to prevent cardiovascular complications. Metreleptin may be an effective treatment for FPLD3.
 This case highlights the importance of early recognition of FPLD syndromes otherwise frequently observed as difficult-to-classify and manages diabetes cases, in order to prevent cardiovascular complications. Metreleptin may be an effective treatment for FPLD3.A large contribution to glucose elimination from the circulation is achieved by insulin-independent processes. We have previously shown that the two incretin hormones, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) increase this process and, therefore, seem to contribute to glucose disposal both through this effect and through the classical incretin effect resulting in enhanced insulin levels. We have now explored in more detail the potential contribution by incretin hormone receptors to insulin-independent processes for glucose elimination. To that end, we have performed intravenous glucose tests (0.35g/kg) in C57BL/6J mice and analyzed glucose elimination rate and glucose effectiveness (i.e., insulin-independent glucose disposal, SG) in wildtype mice and in mice with genetic deletion of GIP receptors or GLP-1 receptors. We performed studies with or without complete blockade of insulin secretion by the drug diazoxide (25 mg/kg). The mice were anesthetized with a novel fentanyl citrate/fluanisone formulation, called Fluafent, together with midazolam. Initially we demonstrated that glucose and insulin data after intravenous and oral glucose were not different using this anesthesia compared to the previously commonly used combination of HypnormR and midazolam. The results show that SG was reduced in GLP-1 receptor knockout mice, whereas there was no difference between GIP receptor knockout mice and wildtype mice, and this was evident both under normal conditions and after complete inhibition of insulin secretion. The study therefore indicates that insulin-independent glucose elimination requires active GLP-1 receptors and thus that the two incretin hormone receptor types show dissociated relevance for this process.Diet-induced gastrointestinal distension is known to evoke satiation and suppress postprandial hyperglycemia; however, the underlying mechanisms remain poorly understood. This study explored how gastrointestinal distension regulates energy homeostasis by using inflating stomach formulation (ISF), the carbonated solution containing pectin that forms stable gel bubbles under acidic condition in the stomach. Here we show that, in mice, oral administration of ISF induced distension of stomach and proximal intestine temporarily, stimulated intestinal glucagon-like peptide-1 (GLP-1) secretion, and activated vagal afferents and brainstem. ISF suppressed food intake and improved glucose tolerance via enhancing insulin sensitivity. The anorexigenic effect was partially inhibited, and the beneficial glycemic effect was blunted by pharmacological GLP-1 receptor blockade and chemical denervation of capsaicin-sensitive sensory nerves. In HFD-fed obese mice showing arrhythmic feeding and obesity, subchronic ISF treatment at the light period (LP) onset for 10 days attenuated LP hyperphagia and visceral fat accumulation. These results demonstrate that gastrointestinal distension by ISF stimulates GLP-1 secretion and the vagal afferent signaling to the brain, thereby regulating feeding behavior and glucose tolerance. Furthermore, subchronic ISF treatment ameliorates HFD-induced visceral obesity. We propose the diet that induces gastrointestinal distension as a novel treatment of hyperphagic obesity and diabetes.The study of the intestinal or gut microbiome is a newer field that is rapidly gaining attention. Bidirectional communication between gut microbes and the host can impact numerous biological systems regulating immunity and metabolism to either promote or negatively impact the host's health. Habitual routines, dietary choices, socioeconomic status, education, host genetics, medical care and environmental factors can all contribute to the composition of an individual's microbiome.  https://www.selleckchem.com/products/ipi-145-ink1197.html  A key environmental factor that may cause negative outcomes is the consumption of nicotine products. The effects of nicotine on the host can be exacerbated by poor dietary choices and together can impact the composition of the gut microbiota to promote the development of metabolic disease including non-alcoholic fatty liver disease. This review explores the contribution of nicotine, poor dietary choices and other unhealthy lifestyle factors to gut dysbiosis.