To understand the underlying pathology of metabolic diseases, such as diabetes, an accurate determination of whole body glucose flux needs to be made by a method that maintains key physiological features. One such feature is a positive differential in insulin concentration between the portal venous and systemic arterial circulation (P/S-IG). P/S-IG during the determination of the relative contribution of liver and extra-liver tissues/organs to whole body glucose flux during an insulin clamp with either systemic (SID) or portal (PID) insulin delivery was examined with insulin infusion rates of 1, 2, and 5 mU·kg(-1)·min(-1) under either euglycemic or hyperglycemic conditions in 6-h-fasted conscious normal rats. A P/S-IG was initially determined with endogenous insulin secretion to exist with a value of 2.07. During an insulin clamp, while inhibiting endogenous insulin secretion by somatostatin, P/S-IG remained at 2.2 with PID, whereas, P/S-IG disappeared completely with SID, which exhibited higher arterial and lower portal insulin levels compared with PID. Consequently, glucose disappearance rates and muscle glycogen synthetic rates were higher, but suppression of endogenous glucose production and liver glycogen synthetic rates were lower with SID compared with PID. When the insulin clamp was performed with SID at 2 and 5 mU·kg(-1)·min(-1) without managing endogenous insulin secretion under euglycemic but not hyperglycemic conditions, endogenous insulin secretion was completely suppressed with SID, and the P/S-IG disappeared. Thus, compared with PID, an insulin clamp with SID underestimates the contribution of liver in response to insulin to whole body glucose flux.
Ten-week-old Zucker diabetic fatty (ZDF) rats at an early stage of diabetes embody metabolic characteristics of obese human patients with type 2 diabetes, such as severe insulin and glucose intolerance in muscle and the liver, excessive postprandial excursion of plasma glucose and insulin, and a loss of metabolic flexibility with decreased lipid oxidation. Metabolic flexibility and glucose flux were examined in ZDF rats during fasting and near-normal postprandial insulinemia and glycemia after correcting excessive postprandial hyperglycemia using treatment with a sodium–glucose cotransporter 2 inhibitor (SGLT2-I) for 7 days. Preprandial lipid oxidation was normalized, and with fasting, endogenous glucose production (EGP) increased by 30% and endogenous glucose disposal (E-Rd) decreased by 40%. During a postprandial hyperglycemic-hyperinsulinemic clamp after SGLT2-I treatment, E-Rd increased by normalizing glucose effectiveness to suppress EGP and stimulate hepatic glucose uptake; activation of glucokinase was restored and insulin action was improved, stimulating muscle glucose uptake in association with decreased intracellular triglyceride content. In conclusion, SGLT2-I treatment improves impaired glucose effectiveness in the liver and insulin sensitivity in muscle by eliminating glucotoxicity, which reinstates metabolic flexibility with restored preprandial lipid oxidation and postprandial glucose flux in ZDF rats.
Disclosure: Nothing to report.KEYWORDS: complementary and alternative medicine, drug toxicity, herbal medication, systemic lupus erythematosus, toxic epidermal necrolysis.A 49-year-old woman with history of rheumatic fever necessitating mechanical mitral valve replacement and a cerebrovascular accident of presumed embolic etiology presented with several months of progressive fatigue, weakness, arthralgias, and myalgias. After an extensive workup, a rheumatologist in the community diagnosed her with systemic lupus erythematosus and dermatomyositis. The patient refused therapy with corticosteroids and disease-modifying agents, citing concerns of adverse effects. She consulted a naturopathic clinician, who gave her Rejuvenator Pills, Super Booster pill, Genesis Juice, and alkaline water (Table 1).Several weeks later, the patient developed dusky erythematous plaques on her anterior and posterior trunk, face, and proximal extremities. Over the next several weeks, she became progressively weak until she was ultimately bedbound. The plaques over her back began to denude. Upon admission to an outside hospital, she was diagnosed with warfarin-related skin necrosis, superinfected decubitus ulcers, and severe anemia. She refused blood transfusion, and was discharged home with clindamycin and iron. After her clinical status deteriorated over the subsequent week, she arrived at our hospital by ambulance.In addition to the herbal medications she had recently started, she had been taking warfarin, furosemide, nitroglycerin via skin patch, and aspirin for over 10 years. On exam, she was febrile, tachycardic, hypotensive, and toxic-appearing. Conjunctivitis was absent. Her mucous membranes were dry, with easily removable white and yellowish deposits on the buccal mucosa. No lesions or ulcerations were present. Dermatologic exam demonstrated confluent scaly, violaceous erythematous patches and plaques covering 60% of the total body surface area with focal areas that were denuded. Large areas of denuded skin were present over the back, inframammary folds, and underneath her abdominal pannus (Figures 1 and 2). Nikolsky's sign was present. She was oriented to person only.Initial laboratory studies were significant for the following: white blood cell count ¼ 12,800 cells/mm 3 , hemoglobin ¼ 7.3 g/dL, creatinine ¼ 11.2 mg/dL, blood urea nitrogen ¼ 136 mg/dL, and bicarbonate level ¼ 15 mmol/L. She was admitted to the medical intensive care unit for presumed sepsis. Aggressive resuscitation and broad spectrum antibiotics were administered. A thorough workup for infection, including blood and urine cultures, chest radiography, and lumbar puncture, was unremarkable. Antinuclear antibodies (ANAs) were present in a 1:2560 titer; with a nucleolar and speckled pattern and cytoplasmic antibodies. Additional rheumatologic workup revealed positive anti-Smith antibody and weakly positive antiribonuclear protein antibody. Pathology from a punch biopsy performed by a dermatology consultant on hospital day 2 demonstrated full-thickness skin necrosis...
According to anecdotal reports in literature, encountering Meckel’s diverticulum in a patient with Crohn’s disease is not uncommon, but differentiating between the overlapping complications of Mickel’s diverticulum and the natural manifestations of Crohn’s disease can be challenging and may impact lifelong therapy. In this report, we present a case of Meckel’s diverticulitis in a patient with stricturing ileocolonic Crohn’s disease. A 29-year-old male has been suffering from recurrent bouts of abdominal pain and diarrhea which were initially thought to be due to recurrent flares of Crohn’s disease. The patient was started on different medical regimens to control his disease, but complete remission was not achieved. He was found to have an inflamed Meckel’s diverticulum during laparotomy with sections of transmural inflammation extending into the diverticulum with absence of heterotopic mucosa. Although Meckel’s diverticulum and Crohn’s disease involve separate disease processes and different pathogenesis, several hypotheses to explain a correlation have been suggested. We believe it is important to consider the presence of an inflamed Meckel’s diverticulum in the differential diagnosis for patients with refractory Crohn’s disease who do not have an adequate response to medical therapy.
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