Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Physical properties of food may account for differences in glycemic and other metabolic responses to food with similar amounts of carbohydrate, fat and protein. Blending of cooked beans made no difference to plasma glucose, insulin, or GIP (gastric inhibitory polypeptide) responses in nondiabetics, NIDD (noninsulin-dependent diabetics), and IDD (insulin-dependent diabetics). The cooked blended beans gave a greater plasma glucose response and a lesser hormonal response than a cooked flummery (containing cornstarch, protein and fat) in nondiabetics. In NIDD and IDD, however, the reverse applied for plasma glucose. In nondiabetics, cooked flummery gave a lesser glycemic response at some time points than uncooked flummery. In NIDD the opposite occurred. Cooking led to no significant change in insulin response in nondiabetics, but to a lesser insulin response in NIDD. The effect of some physical properties of food on diabetic control cannot be inferred from findings in nondiabetics.
 ...
PMID:Food physical factors have different metabolic effects in nondiabetics and diabetics. 299 52

The effect of highly purified natural porcine GIP on C-peptide release was examined in six type I (insulin-dependent) diabetics (IDD) with residual beta-cell function, six type II non-insulin-dependent) diabetics (NIDD), and six normal subjects. All subjects were normal weight. From -120 minutes to 180 minutes glucose or insulin was infused IV to achieve a constant plasma glucose level of 8 mmol/L. On two separate days GIP (2 pmol/kg/min) or isotonic NaCl at random were infused from 0 to 30 minutes. After 10 minutes of GIP infusion plasma IR-GIP concentrations were in the physiologic postprandial range. At 30 minutes a further increase in IR-GIP to supraphysiologic levels occurred. In all subjects plasma, C-peptide increased more after 10 minutes of GIP infusion (IDD, 0.48 +/- 0.05; NIDD, 0.79 +/- 0.11; normal subjects, 2.27 +/- 0.29 nmol/L) than on the corresponding day with NaCl infusion (IDD, 0.35 +/- 0.03; NIDD, 0.62 +/- 0.08; normal subjects, 1.22 +/- 0.13 nmol/L, P less than .05 for all). The responses of the diabetics were significantly lower than that of the normal subjects (P less than .001 for both groups). No further increase in C-peptide occurred during the remaining 20 minutes of the GIP infusion in the diabetic subjects (IDD, 0.49 +/- 0.05; NIDD, 0.83 +/- 0.10 nmol/L). In the presence of a plasma glucose concentration of 8 mmol/L, physiologic concentrations of porcine GIP caused an immediate but impaired beta-cell response in IDD and NIDD patients.
 ...
PMID:Effect of porcine gastric inhibitory polypeptide on beta-cell function in type I and type II diabetes mellitus. 329 36

The literature with respect to GIP is flooded with conflicting data especially with respect to its role in type 2 diabetes mellitus, obesity, type 1 diabetes mellitus and chronic pancreatitis. This review describes possible reasons for the discrepancies which include species variation of GIP, heterogeneity of molecules with different immunoreactivity and bioactivity, deterioration of immunoreactivity of standard and sample on prolonged storage and the effect of the preceding intake of type and quantity of food. The problems can be resolved by raising antibodies to synthetic human GIP and its fragments, the chemical characterization of and the raising of antibodies to immunoreactive GIP 8000, the correct storage of samples and the standard preparation of subjects prior to experimental procedures.
 ...
PMID:Conflicting gastric inhibitory polypeptide data: possible causes. 847 32

This chapter describes a physiological and profound effect of amylin to inhibit meal-related glucagon secretion. Glucagon is processed from a large precursor, proglucagon, in a tissue-specific manner in pancreatic alpha-cells. In addition to amino acid nutrient stimuli, glucagon is also secreted in response to stressful stimuli, such as hypoglycemia and hypovolemia. Glucagon primarily acts on liver to initiate glycogenolysis and gluconeogenesis, resulting in a rapid increase in endogenous production of glucose. With longer stimulation, glucagon action at the liver results in a glucose-sparing activation of free fatty acid oxidation and production of ketones. During hypoglycemia, glucagon secretion is clearly a protective feed-back, defending the organism against damaging effects of low glucose in brain and nerves (neuroglycopenia). Amino acid-stimulated glucagon secretion during meals has a different purpose: amino acids stimulate insulin secretion, which mobilizes amino acid transporters and effects their storage in peripheral tissues. At the same time, insulin obligatorily recruits GLUT4 glucose transporters in muscle and fat. The hypoglycemic potential of such GLUT4 mobilization is averted only by the simultaneous liberation of endogenous glucose in response to feedforward (anticipatory) glucagon secretion. The effect of amylin and its agonists to inhibit amino acid-stimulated glucagon secretion is both potent (EC50 = 18 pM) and profound (approximately 70% inhibition). This glucagonostatic action appears to be extrinsic to the pancreatic islet, occurring in intact animals and in patients, but not in isolated islets or isolated perfused pancreas preparations. On the other hand, the effect of hypoglycemia to stimulate glucagon secretion, which is intrinsic to the islet and occurs in isolated preparations, is not affected by amylin or its agonists. The physiological interpretation of these actions fits with the general concept, illustrated in Fig. 1, that amylin and insulin secreted in response to meals shut down endogenous production as a source of glucose, in favor of that derived from the meal. Amylin and insulin secreted in response to nutrients already absorbed act as a feedback switch for glucose sourcing. The insulinotropic (incretin) gut peptides, GLP-1 and GIP, secreted in response to yet-to-be-absorbed intraluminal nutrients, amplify beta-cell secretion and thereby activate the glucose sourcing switch in a feedforward manner. Hypoglycemia-stimulated glucagon secretion and nutrient (amino acid)-stimulated glucagon secretion are two clearly different processes, differently affected by amylin. The balance of glucose fluxes is disturbed in diabetic states, partly as a result of inappropriate glucagon secretion. Although glucose production due to glucagon secreted in response to hypoglycemia is normal or even reduced in diabetic patients, the secretion of glucagon (and production of endogenous glucose) in response to protein meals is typically exaggerated. Absence of appropriate beta-cell suppression of alpha-cell secretion has been invoked as a mechanism that explains exaggerated glucagon responses, especially prevalent in patients with deficient beta-cell secretion (type 1 diabetes and insulinopenic type 2 diabetes). A proposed benefit of insulin replacement therapy is the reduction of absolute or relative hyperglucagonemia. High glucagon is said to be necessary for ketosis in severe forms of diabetes. A further benefit of reversing hyperglucagonemia is reduction of the excessive endogenous glucose production that contributes to fasting and postprandial hyperglycemia in diabetes. The idea that amylin is a part of the beta-cell drive that normally limits glucagon secretion after meals fits with the observation that glucagon secretion is exaggerated in amylin-deficient states (diabetes characterized by beta-cell failure). This proposal is further supported by the observation that postprandial glucagon suppression is restored following amylin replacement therapy in such states. These observations argue for a therapeutic case for amylin replacement in patients in whom excess glucagon action contributes to fasting and postprandial hyperglycemia and ketosis. The selectivity of amylin's glucagonostatic effect (wherein it is restricted to meal-related glucagon secretion, while preserving glucagon secretion and glucagon action during hypoglycemia) may confer additional benefits; the patient population amenable to amylin replacement therapy is likely to also be receiving insulin replacement therapy, and is thereby susceptible to insulin-induced hypoglycemia. Most explorations of the biology of amylin have used the endogenous hormone in the cognate species (typically rat amylin in rat studies). Clinical studies have typically employed the amylinomimetic agent pramlintide. Studies of amylinomimetic effects on glucagon secretion include effects of rat amylin in anesthetized non-diabetic rats (Jodka et al., 2000; Parkes et al., 1999; Young et al., 1995), effects of rat amylin in isolated perfused rat pancreas (Silvestre et al., 1999), effects of pramlintide in anesthetized non-diabetic rats (Gedulin et al., 1997b,c,d, 1998), effects of pramlintide in patients with type l diabetes (Fineman et al., 1997a,b,c,d, 1998a; Holst, 1997; Nyholm et al., 1996, 1997a,b,c; Orskov et al., 1999; Thompson and Kolterman, 1997), and effects in patients with type 2 diabetes (Fineman et al., 1998b). In addition, effects of amylin antagonists have been observed in isolated preparations (Silvestre et al., 1996), and effects of antagonists or neutralizing antibody have been determined in whole-animal preparations (Gedulin et al., 1997a,e,f).
 ...
PMID:Inhibition of glucagon secretion. 1649 45

The development of incretin-based therapies (glucagon-like peptide 1 [GLP-1] receptor agonists and dipeptidyl peptidase-4 [DPP-4] inhibitors) has changed the landscape of type 2 diabetes management over the past decade. Current developments include longer-acting GLP-1 receptor agonists, fixed-ratio combinations of GLP-1 analogues and basal insulin, as well as implantable osmotic minipumps for long-term delivery of GLP-1 receptor agonists. In longer terms, oral or inhaled GLP-1 analogues may become a reality. In addition, oral enhancers of GLP-1 secretion (e.g. via G-protein-coupled receptors, nuclear farnesoid-receptor X and the G-protein-coupled bile acid-activated receptor [TGR5]) are currently being explored in experimental studies. Combination of GLP-1 with other gut hormones (e.g. peptide YY, glucagon, gastrin, glucose-dependent insulinotropic polypeptide [GIP], secretin, cholecystokinin, vasoactive intestinal polypeptide and pituitary adenylate cyclase-activating polypeptide) may enhance the glucose- and weight-lowering effect of GLP-1 alone, and dual or triple hormone receptor agonists may even exploit the properties of different peptides with just one molecule. There is also an increasing interest in employing incretin-based therapies in other areas, such as type 1 diabetes, impaired glucose metabolism, obesity, polycystic ovary syndrome, non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH), psoriasis or even neurodegeneration. Thus, incretin-based therapies may continue to broaden the therapeutic spectrum for type 2 diabetes and for various other indications in the coming years. This is one of a series of commentaries under the banner '50 years forward', giving personal opinions on future perspectives in diabetes, to celebrate the 50th anniversary of Diabetologia (1965-2015).
 ...
PMID:Incretin-based therapies: where will we be 50 years from now? 2599 73