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M N Feinglos

Publications and source records attributed to M N Feinglos.

At least 37 records · Page 2Linked to original sources
PubMed1995

Impaired second phase insulin response of diabetes-prone C57BL/6J mouse islets.

The C57BL/6J mouse develops obesity and diabetes in response to a high-fat, high-simple carbohydrate diet. To determine the dynamics of glucose-induced insulin release in this animal model of NIDDM, we studied the acute insulin response to glucose of perifused islets in C57BL/6J (diabetes-prone) and A/J (diabetes-resistant) mice fed a normal control diet and of others fed a diabetogenic diet. The insulin response of normal C57BL/6J islets was almost monophasic, with a deficiency in the second phase during high glucose stimulation when compared to that of A/J control islets. The defect in C57BL/6J mice was exaggerated in animals fed a diabetogenic diet. It is suggested that a latent deficiency of second phase insulin release may contribute to the development of the diet-induced syndrome in this model.

Animals↗
PubMed1995

Defective glucose-stimulated insulin release from perifused islets of C57BL/6J mice.

Previous work has shown that the C57BL/6J (BL/6) mouse strain develops type 2 diabetes after being fed a high-fat, high-simple carbohydrate (HFHSC) diet. In contrast, the AJ mouse strain does not. The aim of the present study was to determine if differences in the insulin secretory characteristics of isolated perifused islets of these animals could help explain why the BL/6 mouse develops diet-induced diabetes. Insulin secretion was assessed as mean integrated area under the curve during 20 min of stimulation with 27.7 mM glucose or 5 mM lauric acid. We found that both glucose- and laurate-stimulated insulin secretions were significantly less in euglycemic BL/6 mice than in the euglycemic AJ mice. The defect in insulin response to glucose, but not laurate, in islets from the BL/6 mouse was exacerbated when the animals were fed the HFHSC diet. These data suggest that the BL/6 mouse has a defective insulin response to glucose, which is exacerbated by a diabetogenic diet.

Animals↗
PubMed1994

Glycogen synthase: a putative locus for diet-induced hyperglycemia.

Inbred mouse strains fed a diabetogenic diet have different propensities to develop features analogous to type 2 diabetes mellitus. To define chromosomal locations that control these characteristics, recombinant inbred strains from diabetes-prone C57BL/6J (B/6J) and diabetes-resistant A/J strains were studied. Insulin levels and hyperglycemia correlated with two different regions of mouse chromosome 7 (two point LOD scores > 3.0). For insulin levels, 15 of 16 recombinant inbred strains were concordant with a region that contains the tubby mutation that results in hyperinsulinemia. For hyperglycemia, 19 of 23 strains were concordant with the D7Mit25 marker and 20 of 23 strains with the Gpi-1 locus on proximal mouse chromosome 7. Using more stringent criteria for hyperglycemia, 10 of 11 strains characterized as A/J or B/6J like were concordant with D7Mit25. This putative susceptibility locus is consistent with that of the glycogen synthase gene (Gys) recently suggested as a candidate locus by analyses of type 2 diabetes patients. Fractional glycogen synthase activity in isolated muscle was significantly lower in normal B/6J diabetic-prone mice compared with normal diabetic-resistant A/J mice, a finding similar to that reported in relatives of human patients with type 2 diabetes. These data, taken together, raise the possibility that defects in the Gys gene may in part be responsible for the propensity to develop type 2 diabetes.

Animals↗
PubMed1994

Glycemic response to stress is altered in euglycemic Pima Indians.

The aim of this work was to study the effects of a computer-driven mental arithmetic task on blood glucose in a group of four male and four female euglycemic Caucasians and a group of seven male and six female euglycemic Pima Indians. Approximately 60% of euglycemic Pima Indian Native Americans eventually develop type 2 diabetes, while only 5% of Caucasians develop the disease. All subjects had normal glucose tolerance. Subjects were given a standard breakfast; 2 h later, they were given a computerized mental arithmetic stress test for 10 min. Before, during and after the test, several variables were analyzed, including serum concentrations of glucose, insulin, glucagon and plasma cortisol and catecholamines. Heart rate, systolic and diastolic blood pressure and all the stress hormones increased during stress and decreased during recovery in all subjects. Blood glucose consistently declined one hour after the meal in all subjects. However, while it continued to decline following stress in seven out of eight Caucasian subjects, it consistently increased during and following stress in 10 out of 13 Pima Indians. Fasting serum glucose in Pima Indians and Caucasians was respectively 5.07 + 0.08 mM and 5.04 + 0.09 mM. Two-hour post-prandial values were 5.63 + 0.22 mM and 5.48 + 0.19 mM respectively, whereas post-stress values were 6.15 + 0.19 mM for Pima Indians and 5.22 + 0.20 mM for Caucasians. Both serum glucose means following stress (t = 3.1, P < 0.005) and the direction of change in serum glucose in response to mental arithmetic (chi 2 = 8.2, P < 0.01) clearly differentiated Pimas from Caucasians.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Hypertension in CB57BL/6J mouse model of non-insulin-dependent diabetes mellitus.

The C57BL/6J (BL/6) mouse develops non-insulin-dependent diabetes mellitus (NIDDM) when fed a high fat-high simple carbohydrate (HFHSC) diet, whereas A/J mice do not. The purpose of the study was to determine whether hypertension occurred with NIDDM and whether it was sustained by sympathetic nervous system (SNS) hyperactivity. After 3 mo on an HFHSC diet with a low Na content (0.06%), awake, tail-cuff systolic blood pressure (BP) increased 20% above the control diet in BL/6 (138 +/- 3 vs. 115 +/- 4) but not in A/J (115 +/- 6 vs. 113 +/- 2 mmHg) mice. On a normal Na (0.4%)-HFHSC diet, BL/6 mice had a higher BP than on 0.06% Na (149 +/- 3 at 3 mo, 162 +/- 6 at 4.5 mo). After 1 mo on the 0.06% Na-HFHSC diet, direct BP of anesthetized BL/6 mice was 18% higher than control. The hypotensive response to interruption of SNS activity by ganglionic blockade (chlorisondamine) increased in the BL/6 mice (50%), whereas the heart rate response increased in both strains (20-30%). Analysis of variance (ANOVA) on glucose detected significant effects of strain and diet and a strain x diet interaction (P = 0.0007). At 1 or 3 mo, HFHSC-fed BL/6 mice were hyperglycemic (> 11 mM) compared with diet or strain controls. The ANOVA on insulin detected strain and diet effects but not a strain x diet interaction (P = 0.3). HFHSC increased insulin above the control of 140-160 pM in A/J and BL/6 strain (20-70% at 1 mo, 400% at 3 mo).(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia↗
PubMed1993

Relaxation training for NIDDM. Predicting who may benefit.

OBJECTIVE: To examine the benefits of relaxation training for patients with NIDDM and to investigate individual differences that could predict a positive response to relaxation training. RESEARCH DESIGN AND METHODS: Thirty-eight subjects with NIDDM were treated with intensive conventional diabetes therapy after an initial metabolic evaluation and psychological and pharmacological testing. Half were assigned to also receive biofeedback-assisted relaxation training. Treatment effects on GHb levels and glucose tolerance were evaluated after 8 wk. RESULTS: Subjects demonstrated significant improvements in GHb level, but not in glucose tolerance, after 8 wk of intensive conventional treatment. These improvements persisted throughout the follow-up period. However, the group provided with relaxation training did not experience greater improvements on either measure than the group given conventional diabetes treatment only. Within the group that received relaxation training, correlations occurred between the improvements in glucose tolerance after treatment and individual differences in trait anxiety and in the effect of alprazolam on glucose tolerance. Differences in the effects of EPI on glucose tolerance and personality measures of neuroticism and perceived locus of control also appeared to be related to improvements in glucose tolerance after training. CONCLUSIONS: Relaxation training did not confer added benefit over and above that provided by conventional diabetes treatment for patients with NIDDM. Additional research is needed to determine whether the administration of relaxation training to selected patients, especially those who are most responsive to stress, would provide benefits for glucose control that are not achieved by conventional treatment.

Analysis of Variance↗
PubMed1992

Stress and diabetes mellitus.

Stress is a potential contributor to chronic hyperglycemia in diabetes. Stress has long been shown to have major effects on metabolic activity. Energy mobilization is a primary result of the fight or flight response. Stress stimulates the release of various hormones, which can result in elevated blood glucose levels. Although this is of adaptive importance in a healthy organism, in diabetes, as a result of the relative or absolute lack of insulin, stress-induced increases in glucose cannot be metabolized properly. Furthermore, regulation of these stress hormones may be abnormal in diabetes. However, evidence characterizing the effects of stress in type I diabetes is contradictory. Although some retrospective human studies have suggested that stress can precipitate type I diabetes, animal studies have shown that stressors of various kinds can precipitate--or prevent--various experimental models of the disease. Human studies have shown that stress can stimulate hyperglycemia, hypoglycemia, or have no affect at all on glycemic status in established diabetes. Much of this confusion may be attributable to the presence of autonomic neuropathy, common in type I diabetes. In contrast, more consistent evidence supports the role of stress in type II diabetes. Although human studies on the role of stress in the onset and course of type II diabetes are few, a large body of animal study supports the notion that stress reliably produces hyperglycemia in this form of the disease. Furthermore, there is mounting evidence of autonomic contributions to the pathophysiology of this condition in both animals and humans.

Animals↗
PubMed1992

Screening for microalbuminuria. A comparison of single sample methods of collection and techniques of albumin analysis.

OBJECTIVE: To evaluate single-sample urine collections to determine their ability to screen patients for the presence of microalbuminuria. Microalbuminuria in patients with type I diabetes predicts the development of diabetic renal disease. RESEARCH DESIGN AND METHODS: Cross-sectional analysis of single-sample urine collection techniques (first morning void, random upright void) and methods of albumin analysis (RIA, reagent tablet) were compared with conventional 24-h urine collections (RIA). The study included 94 patients (45 males, 49 females; mean serum creatinine 88 microM) with type I diabetes, selected from a screened population of 301 patients from the University Hospital Subspecialty Clinics. RESULTS: A 24-hour urine collection RIA analysis for albumin revealed 36 normal patients (< 30 mg), 27 with microalbuminuria (30-300 mg), and 31 with albuminuria (> 300 mg). Random upright urine samples were more sensitive (RIA 89%, tablets 78%) for the detection of microalbuminuria than first morning void specimens (RIA 70%, tablets 60%). Specificity was > 80% with both random and first morning voids. CONCLUSIONS: Screening for microalbuminuria can be performed in the clinic by random upright single-sample urine collections. When reagent tablets were used, these results are available immediately. Patients who screen positive should be confirmed by 24-h or other timed urine collections.

Adult↗
PubMed1991

Control of expression of insulin resistance and hyperglycemia by different genetic factors in diabetic C57BL/6J mice.

The inheritance of the tendency to develop diet-induced non-insulin-dependent (type II) diabetes was analyzed in crosses between diabetes-prone C57BL/6J (BL/6) mice and diabetes-resistant A/J mice. The effects of a diabetogenic diet on blood glucose and insulin levels, insulin sensitivity, and weight were evaluated in F1 and both (BL/6 X A/J) F1 X BL/6 and (BL/6 X A/J) F1 X A/J backcross mice. These results suggest that diet-induced hyperglycemia is largely determined by a recessive gene and diet-induced insulin resistance by a dominant gene. Analyses of both backcrosses indicated that insulin sensitivity and blood glucose levels were unrelated, suggesting that they are controlled by different genetic factors. This conclusion was supported by data from nine recombinant inbred BXA strains in which no correlation was observed between these variables. Furthermore, insulin sensitivity and body weight correlated differently in the two backcross groups, suggesting that insulin resistance is not simply a function of obesity. The number of genes that predominantly influence diabetic traits was estimated by comparing the variance observed in (BL/6 X A/J) F1 X BL/6 backcross mice with that observed in parental mice. The data suggest that relatively few genes predominantly affect the diabetic phenotype in this murine model.

Animals↗
PubMed1989

Differential glycemic effects of morphine in diabetic and normal mice.

C57BL/6J ob/ob mice, C57BL/6J+/? lean mice and A/J mice were given injections of 10 mg/kg of morphine or an equal volume of saline, and then blood was sampled by retroorbital sinus puncture. In addition, animals from each strain were exposed to a brief experimental stress ten minutes after the administration of morphine or saline. While morphine produced significant increases in serum glucose in albino mice, morphine lowered blood insulin in both C57BL/6J ob/ob and C57BL/6J+/? mice. Morphine significantly lowered blood insulin in A/J mice, but effects in C57BL/6J mice were not significant. In contrast, morphine attenuated blood glucose and insulin during stress in C57BL/6J ob/ob but did not significantly affect either glucose or insulin during stress in lean C57BL/6J or A/J mice. These results are interpreted in the light of other data suggesting that endogenous opiates modulate the effects of sympathetic nervous system activity in type II diabetes.

Animals↗
PubMed1989

Muscarinic stimulation and antagonism and glucoregulation in nondiabetic and obese hyperglycemic mice.

Plasma glucose and insulin responses to a muscarinic agonist (bethanechol chloride) and a muscarinic antagonist (atropine) were evaluated in obese C57BL/6J ob/ob mice and in lean C57BL/6J + /? mice. In lean +/? mice, plasma glucose decreased in response to 1 and 2 micrograms/g bethanechol chloride, whereas insulin increased significantly. In ob/ob mice, insulin increased remarkably in response to bethanechol administration (saline, 632 +/- 80 microU/ml; 2 micrograms/g bethanechol chloride, 1794 +/- 97 microU/ml; n = 10), but surprisingly, plasma glucose also rose significantly (saline, 230 +/- 14 mg/dl; 2 micrograms/g bethanechol chloride, 363 +/- 18 mg/dl, n = 10). This exaggerated hyperglycemia in ob/ob mice was not associated with significant changes in plasma glucagon. Furthermore, administration of propranolol hydrochloride did not diminish bethanechol chloride-induced hyperglycemia in ob/ob mice. Administration of atropine (2.5, 5, and 10 mg/kg body wt) induced a significant decrease in plasma insulin without changes in plasma glucose in ob/ob mice, whereas neither plasma insulin nor plasma glucose changed in lean mice. Finally, conversion of [14C]alanine to glucose was increased in ob/ob mice after bethanechol chloride administration, indicating that muscarinic stimulation increases gluconeogenesis in an animal model of type II (non-insulin-dependent) diabetes.

Animals↗
PubMed1988

Diet-induced type II diabetes in C57BL/6J mice.

We investigated the effects of diet-induced obesity on glucose metabolism in two strains of mice, C57BL/6J and A/J. Twenty animals from each strain received ad libitum exposure to a high-fat high-simple-carbohydrate diet or standard Purina Rodent Chow for 6 mo. Exposure to the high-fat, high-simple-carbohydrate, low-fiber diet produced obesity in both A/J and C57BL/6J mice. Whereas obesity was associated with only moderate glucose intolerance and insulin resistance in A/J mice, obese C57BL/6J mice showed clear-cut diabetes with fasting blood glucose levels of greater than 240 mg/dl and blood insulin levels of greater than 150 microU/ml. C57BL/6J mice showed larger glycemic responses to stress and epinephrine in the lean state than AJ mice, and these responses were exaggerated by obesity. These data suggest that the C57BL/6J mouse carries a genetic predisposition to develop non-insulin-dependent (type II) diabetes. Furthermore, altered glycemic response to adrenergic stimulation may be a biologic marker for this genetic predisposition to develop type II diabetes.

Animals↗
PubMed1987

Exaggerated peripheral responses to catecholamines contributes to stress-induced hyperglycemia in the ob/ob mouse.

The present study investigated the contribution of altered sympathetic reactivity to the stress-induced hyperglycemia observed in the c57BL/6J (ob/ob) mouse, an animal model of type II diabetes. Blood glucose and insulin responses to sympathetic agonist and antagonist administration were evaluated in ob/ob mice and their nondiabetic, lean (ob/?) littermates. In addition, the ability of nutritional status to modify these responses was determined. These studies demonstrated that epinephrine administration to ob/ob mice caused an exaggerated increase in blood glucose and decrease in plasma insulin in ob/ob mice relative to lean littermates. The dose response curve for epinephrine-induced increases in blood glucose were shifted to the left, and the duration of the blood glucose and plasma insulin responses was longer. Differences between ob/ob mice and their nondiabetic littermates were greater when animals were tested in the fasted state. In addition, administration of the alpha adrenergic antagonist phentolamine caused a larger increase in plasma insulin in ob/ob mice than was observed in lean littermates. These results suggest that altered peripheral responses to sympathetic stimuli contribute to stress-induced hyperglycemia in ob/ob mice, and raise the possibility that altered sympathetic function is an etiologic factor in development of diabetes in these animals.

Adrenergic Fibers↗