ABSTRACT
Chronic cold exposure stimulates sympathetically driven thermogenesis in brown adipose tissue (BAT), resulting in fat mobilization, weight loss, and compensatory hyperphagia. Hypothalamic neuropeptide Y (NPY) neurons are implicated in stimulating food intake in starvation, but may also suppress sympathetic outflow to BAT. This study investigated whether the NPY neurons drive hyperphagia in rats that have lost weight through cold exposure. Rats exposed to 4 degrees C for 21 days weighed 14% less than controls maintained at 22 degrees C (P < 0.001). Food intake increased after 3 days and remained 10% higher thereafter (P < 0.001). Increase BAT activity was confirmed by 64, 96, and 335% increases in uncoupling protein-1 mRNA at 2, 8, and 21 days. Plasma leptin decreased during prolonged cold exposure. Cold-exposed rats showed no significant changes in NPY concentrations in any hypothalamic regions or in hypothalamic NPY mRNA at any time. We conclude that the NPY neurons are not activated during cold exposure. This is in contrast with starvation-induced hyperphagia, but is biologically appropriate since enhanced NPY release would inhibit thermogenesis causing potentially lethal hypothermia. Other neuronal pathways must therefore mediate hyperphagia in chronic cold exposure.
Subject(s)
Acclimatization , Body Temperature Regulation , Feeding Behavior , Hyperphagia/physiopathology , Hypothalamus/physiopathology , Neuropeptide Y/metabolism , Proteins/metabolism , Animals , Body Weight , Cold Temperature , Hypothalamus/metabolism , Leptin , Male , Neurons/physiology , Neuropeptide Y/biosynthesis , Obesity , RNA, Messenger/biosynthesis , Rats , Rats, Wistar , Time Factors , Transcription, GeneticABSTRACT
Insulin receptors differing structurally from those in other tissues have been demonstrated in brain from many species. Subtle differences in binding properties have been reported between insulin receptors in brain and other tissues, including differences in affinity of pig brain receptors for human and porcine insulin. Insulin binding has been demonstrated in human cerebral cortex, but insulin binding has not been characterized in other areas of human brain. We have studied the binding of 125I labelled human insulin, and its displacement by unlabelled human and porcine insulin, in homogenates prepared from human hypothalamus, cerebral cortex and cerebellum obtained post-mortem from eight non-diabetic subjects. Specific binding was demonstrated in all brain regions studied, and displacement curves obtained with unlabelled human and porcine insulin were identical. By contrast, unlabelled insulin-like growth factor-1 did not significantly displace 125I labelled human insulin over the same concentration range. We therefore conclude that insulin receptors are widely distributed in human brain and do not differ in their affinity for human and porcine insulin.
Subject(s)
Brain Chemistry/physiology , Brain/metabolism , Insulin/metabolism , Membrane Proteins/metabolism , Receptor, Insulin/analysis , Aged , Aged, 80 and over , Animals , Autopsy , Binding, Competitive , Brain/anatomy & histology , Brain/pathology , Dose-Response Relationship, Drug , Female , Humans , Insulin/analysis , Insulin-Like Growth Factor I/pharmacology , Iodine Radioisotopes , Male , Middle Aged , Receptor, Insulin/metabolism , SwineABSTRACT
OBJECTIVE: To control insulin-induced edema in a patient with poorly controlled IDDM. RESEARCH DESIGN AND METHODS: A 31-yr-old woman with a 14-yr history of poorly controlled IDDM first developed peripheral edema 3 yr after diagnosis of IDDM; the edema worsened whenever insulin dosage was increased. In August 1991, severe edema developed after treatment of ketoacidosis, with body weight increasing from 46 to 61 kg. No evidence of cardiac dysfunction or autonomic neuropathy existed, and serum albumin was consistently normal. RESULTS: Treatment with 15 mg of ephedrine every 8 h produced a prompt diuresis, with body weight falling by 4 kg in 48 h and by 12 kg within 1 wk. CONCLUSIONS: Ephedrine may be an effective treatment for insulin-induced edema and may be preferable to the use of diuretics in such patients.
Subject(s)
Diabetes Mellitus, Type 1/drug therapy , Edema/chemically induced , Edema/drug therapy , Ephedrine/therapeutic use , Insulin/adverse effects , Adult , Dose-Response Relationship, Drug , Female , Humans , Insulin/therapeutic useABSTRACT
An automated method for the optimal placement of polar hydrogens in a protein structure is described. This method treats the polar, side chain hydrogens of lysine, serine, threonine, and tyrosine and the amino terminus of a protein. The program, called NETWORK, divides the potential hydrogen-bonding pairs of a protein into groups of interacting donors and acceptors. A search is conducted on each of the local groups to find an arrangement which forms the most hydrogen bonds. If two or more arrangements have the same number of hydrogen bonds, the arrangement with the shortest set of hydrogen bonds is selected. The polar hydrogens of the histidyl side chain are specifically treated, and the ionization state of this residue is allowed to change, if this change results in additional hydrogen bonds for the local group. The program will accept Protein Data Bank as well as Biosym-format coordinate files. Input and output routines can be easily modified to accept other coordinate file formats. The predictions from this method are compared to known hydrogen positions for bovine pancreatic trypsin inhibitor, insulin, RNase-A, and trypsin for which the neutron diffraction structures have been determined. The usefulness of this program is further demonstrated by a comparison of molecular dynamics simulations for the enzyme cytochrome P-450cam with and without using NETWORK.
