Involvement of Glucagon in Preventive Effect of Menthol Against High Fat Diet Induced Obesity in Mice.

Glucagon mediated mechanisms have been shown to play clinically significant role in energy expenditure. The present study was designed to understand whether pharmacological mimicking of cold using menthol (TRPM8 modulator) can induce glucagon-mediated energy expenditure to prevent weight gain and related complications. Acute oral and topical administration of TRPM8 agonists (menthol and icilin) increased serum glucagon concentration which was prevented by pre-treatment with AMTB, a TRPM8 blocker.

Isomalto-oligosaccharides, a prebiotic, functionally augment green tea effects against high fat diet-induced metabolic alterations via preventing gut dysbacteriosis in mice.

High fat diet (HFD)-induced alterations in gut microbiota and resultant 'leaky gut' phenomenon promotes metabolic endotoxemia, ectopic fat deposition, and low-grade systemic inflammation. Here we evaluated the effects of a combination of green tea extract (GTE) with isomalto-oligosaccharide (IMOs) on HFD-induced alterations in mice. Male Swiss albino mice were fed with HFD (58% fat kcal) for 12 weeks.

A novel cobiotic-based preventive approach against high-fat diet-induced adiposity, nonalcoholic fatty liver and gut derangement in mice.

Background: High-fat diets (HFDs) induce systemic inflammation, gut microbial derangements and disturb metabolic homeostasis, resulting in weight gain, insulin resistance and nonalcoholic fatty liver (NAFL). Numerous antioxidants and prebiotic/probiotics per se may prevent HFD-associated comorbidities, but there are no reports related to their combination.

Objective: In the present study, we aim to evaluate a cobiotic combination of lycopene (antioxidant) and isomalto-oligosaccharides (IMOs, a prebiotic) for prevention of HFD-induced alterations.

Resistance to the Beneficial Metabolic Effects and Hepatic Antioxidant Defense Actions of Fibroblast Growth Factor 21 Treatment in Growth Hormone-Overexpressing Transgenic Mice.

Fibroblast growth factor 21 (FGF21) modulates a diverse range of biological functions, including glucose and lipid metabolism, adaptive starvation response, and energy homeostasis, but with limited mechanistic insight. FGF21 treatment has been shown to inhibit hepatic growth hormone (GH) intracellular signaling. To evaluate GH axis involvement in FGF21 actions, transgenic mice overexpressing bovine GH were used.

Specific suppression of insulin sensitivity in growth hormone receptor gene-disrupted (GHR-KO) mice attenuates phenotypic features of slow aging.

In addition to their extended lifespans, slow-aging growth hormone receptor/binding protein gene-disrupted (knockout) (GHR-KO) mice are hypoinsulinemic and highly sensitive to the action of insulin. It has been proposed that this insulin sensitivity is important for their longevity and increased healthspan. We tested whether this insulin sensitivity of the GHR-KO mouse is necessary for its retarded aging by abrogating that sensitivity with a transgenic alteration that improves development and secretory function of pancreatic β-cells by expressing Igf-1 under the rat insulin promoter 1 (RIP::IGF-1).

Preservation of blood glucose homeostasis in slow-senescing somatotrophism-deficient mice subjected to intermittent fasting begun at middle or old age.

Poor blood glucose homeostatic regulation is common, consequential, and costly for older and elderly populations, resulting in pleiotrophically adverse clinical outcomes. Somatotrophic signaling deficiency and dietary restriction have each been shown to delay the rate of senescence, resulting in salubrious phenotypes such as increased survivorship. Using two growth hormone (GH) signaling-related, slow-aging mouse mutants we tested, via longitudinal analyses, whether genetic perturbations that increase survivorship also improve blood glucose homeostatic regulation in senescing mammals.

Interaction of growth hormone receptor/binding protein gene disruption and caloric restriction for insulin sensitivity and attenuated aging.

The correlation of physiological sensitivity to insulin ( vis-à-vis glycemic regulation) and longevity is extensively established, creating a justifiable gerontological interest on whether insulin sensitivity is causative, or even predictive, of some or all phenotypes of slowed senescence (including longevity). The growth hormone receptor/ binding protein gene-disrupted (GHR-KO) mouse is the most extensively investigated insulin-sensitive, attenuated aging model. It was reported that, in a manner divergent from similar mutants, GHR-KO mice fail to respond to caloric restriction (CR) by altering their insulin sensitivity.

Changing paradigms in type 2 diabetes mellitus.

Diabetes mellitus has been increasing in prevalence and imposes serious economic burdens on both the developed as well as the developing world. Understanding pathobiological underpinning of chronic progressive disease like diabetes is an imperative that we cannot escape. For several decades now, the focus has remained on a two hit theory which begins with insulin resistance and is followed thereafter by the β cell failure.

Recombinant human parathyroid hormone therapy (1-34) in an adult patient with a gain-of-function mutation in the calcium-sensing receptor-a case report.

Objective: To describe a case of hypocalcemia in a patient with a gain-of-function mutation in the calcium-sensing receptor that was undetected until adulthood and successfully treated with recombinant parathyroid hormone.

Methods: The clinical findings, laboratory data, and a review of the pertinent literature are presented.

Results: A 55-year-old woman was hospitalized and seen by the endocrinology consult service for hypocalcemia that was refractory to repeated doses of intravenous calcium gluconate.

Endocrine and metabolic changes during sepsis: an update.

The authors have reviewed the most recent and relevant literature from which reasonable conclusions may be drawn. This article highlights important endocrine and metabolic changes, and provides possible explanations for observed perturbations. Obviously infectious disease specialists are not charged with the primary responsibility of addressing these issues, which have largely remained the domain of endocrinologists and intensivists.

Glucose control and cardiovascular outcomes: reorienting approach.

Cardiovascular disease accounts for nearly 70% of morbidity and mortality in patients with diabetes mellitus. Strides made in diabetes care have indeed helped prevent or reduce the burden of microvascular complications in both type 1 and type 2 diabetes. However, the same cannot be said about macrovascular disease in diabetes.

A pituitary abscess masquerading as recurrent hypernatremia and aseptic meningitis.

Pituitary abscess is a rare condition. In the setting of multiple surgical interventions, the risk of its development increases. A 49-year-old man presented with episodes of altered mental status.

Immunotherapy in miscellaneous medical disorders Graves ophthalmopathy, asthma, and regional painful syndrome.

In Graves ophthalmopathy, immunotherapy is offering an opportunity of reducing bad outcomes that lead to disfigurement and impairment of vision. These therapies are not perfect; however, we now have a chance to achieve better outcomes. In asthma, immune therapy using passive immunity targeting key proinflammatory cytokine/chemokines and medications of their effects has opened an avenue of research into a safe and durable therapy.

Biologic response modifiers: relevance & repercussions.

Biologic response modifiers (BRMs) are substances that occur naturally in the body. They can also be manufactured in the laboratory and then administered as targeted therapy. Undoubtedly BRMs will find expanded role in terminal illness like cancer where other therapies have failed.

Glucose homeostasis and insulin sensitivity in growth hormone-transgenic mice: a cross-sectional analysis.

In contrast to its stimulatory effects on musculature, bone, and organ development, and its lipolytic effects, growth hormone (GH) opposes insulin effects on glucose metabolism. Chronic GH overexposure is thought to result in insulin insensitivity and decreased blood glucose homeostatic control. Yet, despite the importance of this concept for basic biology, as well as human conditions of GH excess or deficiency, no systematic assessment of the impact of GH over- expression on glucose homeostasis and insulin sensitivity has been conducted.

Insulin-like growth factor-1 receptor activation prevents high glucose-induced mitochondrial dysfunction, cytochrome-c release and apoptosis.

Vascular disease is the leading cause of morbidity and mortality in patients with diabetes. Persistent hyperglycemia--the dominant metabolic derangement of diabetes, can cause endothelial cell apoptosis. Diabetes is often associated with low insulin like growth factor-1 (IGF-1), and the latter state has been linked to adverse risk profile and increased cardiovascular disease incidence.

Influence of TRPV1 on diabetes-induced alterations in thermal pain sensitivity.

A common complication associated with diabetes is painful or painless diabetic peripheral neuropathy (DPN). The mechanisms and determinants responsible for these peripheral neuropathies are poorly understood. Using both streptozotocin (STZ)-induced and transgene-mediated murine models of type 1 diabetes (T1D), we demonstrate that Transient Receptor Potential Vanilloid 1 (TRPV1) expression varies with the neuropathic phenotype.

Infections in diabetes mellitus and hyperglycemia.

Infections in diabetes mellitus are relatively more common and serious. Diabetic patients run the risk of acute metabolic decompensation during infections, and conversely patients with metabolic decompensation are at higher risk of certain invasive infections. Tight glycemic control is of paramount importance during acute infected or high stress state.

Infection, immunity, and hormones/endocrine interactions.

Infections and stress, immune responses, and hormones are interconnected, ensuring immune competence to deal with immediate threat of overwhelming infection and metabolic collapse. Emergence of cytokines as key signal mediators and appreciation of autocrine-paracrine influences of hormones have helped explain how signals are transmitted and responses evoked. This has led to possibilities of creating therapies that might be used to enhance protective signals and dampen signals emanating from host and invading organism interaction that might otherwise be detrimental.

Transient ischemic attack and nephrotic syndrome: Case report and review of literature.

Thrombotic complications in patients with nephrotic syndrome are attributed to a hypercoagulable state. Venous thrombosis is common, but arterial thrombosis occurs less frequently in adult nephrotic patients. We report a case of recurrent transient ischemic attacks as an initial manifestation of nephrotic syndrome due to early-stage membranous glomerulonephritis, review the literature for similar cases, and briefly discuss this potentially life-threatening condition.

Hyperparathyroidism and multiple endocrine neoplasia.

Multiple endocrine neoplasia (MEN) syndromes comprise the group of heritable endocrinopathies, MEN 1, MEN 2A, and MEN 2B. Primary hyperparathyroidism caused by multiglandular involvement is usually the initial manifestation in MEN 1, occurring in more than 90% of patients. In patients with MEN 2A, hyperparathyroidism develops less commonly and is usually milder than in MEN 1.

Hyperparathyroid crisis manifesting as respiratory and heart failure.

Objective: To describe a case of hyperparathyroid crisis manifesting as respiratory failure and congestive heart failure and to emphasize the implications of hypercalcemia and hypophosphatemia in this setting.

Methods: A case report and a review of the pertinent literature are presented.

Results: A 71-year-old man was transferred to our care because of respiratory failure and congestive heart failure.